Endocrine Disruptors: Is it Time to Act

Endocrine Disruptors: Is it Time to Act ? Christian A. Koch, MD, PhD January 21, 2015

Objectives 1. Review various substances known to act as endocrine disruptors 2. Understand how bisphenol A, dioxins, polybrominated diphenyl ether, pesticides, phtalates, polychlorinated biphenyls, and heavy metals can affect the endocrine and other body systems

In the peaceful Appalachian hills of eastern Kentucky, toxins are being dumped into abandoned mines, causing environmental havoc, but the locals, mindful of their jobs and the power of the mine owners, can do nothing. EPA CID agent Jack Taggart (Steven Seagal) is sent to investigate, after a fellow agent is found dead, probably not by accident. The EPA has received an anonymous letter from the town of Jackson, Kentucky, and Taggart goes there undercover to continue his colleague's investigations. It is discovered that Hanner Coal Company is being paid to dump toxic waste into an abandoned coal mine shaft, so Jack is assigned to go to the small town of Jackson. He stays in a room in the church's basement, and begins his cover work by repairing the roof at a house where one of the children is sick because of the pollution. He attempts to question the family, but they do not have much to say. He has little better results elsewhere; even the man who tipped off the EPA is decidedly taciturn.

http://www.youtube.com/watch?v=2yVoHp1dUvg

Exxon Valdez 1989 A figure of 11 million US gallons was a commonly accepted estimate of the spill's volume and has been used by the State of Alaska's Exxon Valdez Oil Spill Trustee Council,[5] the National Oceanic and Atmospheric Administration and environmental groups such as Greenpeace and the Sierra Club. Some twenty years after the spill, a team from the University of North Carolina found that the effects were lasting far longer than expected.[27] The team estimates some shoreline Arctic habitats may take up to thirty years to recover. Exxon Mobil denies any concerns over this, stating that they anticipated a remaining fraction that they assert will not cause any long-term ecological impacts, according to the conclusions of 350 peer-reviewed studies.[28] However, a NOAA study concluded that this contamination can produce chronic low-level exposure, discourage subsistence where the contamination is heavy, and decrease the "wilderness character" of the area.

http://en.wikipedia.org/wiki/List_of_nuclear_reactors

Safety ? - Earthquakes - Sinkholes - etc.

Corrosion is the gradual destruction of materials (usually metals) by chemical reaction with their environment. In the most common use of the word, this means electrochemical oxidation of metals in reaction with an oxidant such as oxygen. Rusting, the formation of iron oxides, is a wellknown example of electrochemical corrosion. This type of damage typically produces oxide(s) or salt(s) of the original metal.

Mol Endocrinol 2015

• Bisphenol A • Phtalates • Dioxins • DDT/DDE (pesticides) • Vinclozolin (fungicide) , antiandrogenic on fruits • Triclosan (antibacterial in soaps) • DES

Pollution cocktail

• PCBs / polychlorinated biphenyls • PPDEs (flame retardants) • Genistein • Heavy metals •PFOAs (perfluoroalkyl acids) Teflon /thyroid cancer

600 ingredients. When burned, cigarettes create more than 7,000 chemicals. At least 69 of these chemicals are known to cause cancer, and many are poisonous. American Lung Many of these chemicals are also found in consumer products, but these products have warning labels. There is no such warning for Association the toxins in tobacco smoke. A few of the chemicals in tobacco smoke, and other places they are found: What is in a Cigarette ? Acetone – found in nail polish remover Acetic Acid – an ingredient in hair dye Ammonia – a common household cleaner Arsenic – used in rat poison Benzene – found in rubber cement Butane – used in lighter fluid Cadmium – active component in battery acid Carbon Monoxide – released in car exhaust fumes Formaldehyde – embalming fluid Hexamine – found in barbecue lighter fluid Lead – used in batteries Naphthalene – an ingredient in moth balls Methanol – a main component in rocket fuel Nicotine – used as insecticide Tar – material for paving roads Toluene - used to manufacture paint

Smoking Cars ? Emission control ? Vehicle emissions control is the study of reducing the motor vehicle emissions—emissions produced by motor vehicles, especially internal combustion engines. Emissions of many air pollutants have been shown to have variety of negative effects on public health and the natural environment. Emissions that are principal pollutants of concern include: •Hydrocarbons - A class of burned or partially burned fuel, hydrocarbons are toxins. Hydrocarbons are a major contributor to smog, which can be a major problem in urban areas. Prolonged exposure to hydrocarbons contributes to asthma, liver disease, lung disease, and cancer. Regulations governing hydrocarbons vary according to type of engine and jurisdiction; in some cases, "non-methane hydrocarbons" are regulated, while in other cases, "total hydrocarbons" are regulated. Technology for one application (to meet a nonmethane hydrocarbon standard) may not be suitable for use in an application that has to meet a total hydrocarbon standard. Methane is not directly toxic, but is more difficult to break down in a catalytic converter, so in effect a "non-methane hydrocarbon" regulation can be considered easier to meet. Since methane is a greenhouse gas, interest is rising in how to eliminate emissions of it. •Particulate matter – Soot or smoke made up of particles in the micrometre size range: Particulate matter causes negative health effects, including but not limited to respiratory disease and cancer.

Endocrine Disruptor – coined at Wingspread Conference Center in 1991 Theo Colborn is Founder and President of The Endocrine Disruption Exchange (TEDX), based in Paonia, Colorado, and Professor Emeritus of Zoology at the University of Florida, Gainesville. She is an environmental health analyst, and best known for her studies on the health effects of endocrine disrupting chemicals.

Colorado potato beetle on crops DDT / Dichloro-diphenyltrichloroethane first used as a pesticide in 1936

Goodman & Gilman’s . The Pharmacological Basis of Therapeutics, 12th edition, McGraw Hill, 2011

Poisons move up the food chain • At each trophic level, chemical concentration increases: biomagnification

• DDT concentrations increase from plankton to fish to fish-eating birds

Figure 10.9

Global Transport of Persistent Organic Pollutants








LDDI Consensus Statement Scientific Consensus Statement on Environmental Agents Associated with Neurodevelopmental Disorders Developed by the Collaborative on Health and the Environment’s Learning and Developmental Disabilities Initiative February 20, 2008 (revised July 1, 2008)

http://www.iceh.org/LDDI.html

What we don’t know about chemicals ~10 we know for sure ~200 with good evidence ~1,000 suspected More than 80,000 unknown

Environmental Contributors to Disorders • Timing of exposure • Bioaccumulation and mixtures • Mechanisms of disruption • Variable sensitivity • Evidence of exposures (body burden)

• Persistent chemicals

Timing of exposure A child’s developing nervous system is more sensitive to chemical exposures than the adult nervous system

Environmental Agents Environmental agents that we are confident cause learning and developmental disabilities in humans

Alcohol Lead Mercury PCBs PBDEs Manganese

Arsenic Solvents PAHs Pesticides Nicotine & ETS

Lead • There is no safe level of lead exposure for children • Even the lowliest of lead exposure cause impairs overall intelligence as measured by IQ, learning and memory

Rationale for Lowering the Blood Lead Action Level From 10 to 2 µg/dl. Steven G. Gilbert and Bernard Weiss. Neurotoxicology Vol 27/5, September 2006, pp 693-701.

Acceptable Childhood Blood Lead Levels 60

Blood Lead (ug/dl)

• The CDC should lower the blood lead action level

60

50

40

40

30

30

25 20

20

15 10

10

2 0 CDC 1960

CDC 1973

CDC 1975

CDC 1985

WHO 1986

EPA 1986

Agency and Year

CDC 1990

CDC When?

Mercury • Mercury bioaccumulates in fish • Mercury is distributed in the environment by coal burning electric utility plants • Mercury advisories limit fish consumption for women and children • US EPA RfD 0.1 ug/dL

PCBs - Polychlorinated biphenyls • Highly persistent and bioaccumulative • Stored in fat and excreted in women’s breast milk • Exposure can adversely affect motor skills, learning and memory as shown in lower fullscale and verbal IQ scores and reading ability

PBDEs - Polybrominated diphenyl ethers • Commonly used as flame-retardant • PBDEs, structurally similar to PCBs • Bioaccumulates in animals and humans, and are excreted in human breast milk • Developmental neurotoxicants O

Brx

Bry

Manganese • Manganese is a trace element which is necessary in small amounts for growth and development • High levels of manganese exposure, from inhalation (welding fumes) or through drinking water, can damage the developing nervous system as measured in full-scale IQ and verbal • US EPA water levels of manganese should not exceed 300 μg Mn/L

Arsenic • Commonly found in drinking water around the world, sometimes in concentrations high enough to cause cancer

• Dose-response relationship between exposure to arsenic and intellectual impairment

Sci Rep. 2013;3:2195. doi: 10.1038/srep02195

Solvents • Broad array of different compounds including toluene, benzene, alcohol, turpentine, acetone and tetrachloroethylene (TCE)

• More than 50 million metric tons used in the US and more than 10 million people exposed in the workplace

PAHs - Polycyclic aromatic hydrocarbons • Widely distributed air pollutants and well-recognized human mutagens and carcinogens

• PAHs are generated during combustion of fuels from motor vehicles, coal-fired power plants, residential heating, cooking, and tobacco smoke • PAHs results in lower birth weight and affects cognitive development

Pesticides • Designed to kill insects, plants, fungi or animals

• Agricultural and residential application of pesticides in the US totals more than one billion pounds per year • Childhood exposure enhances the risk for developmental disorders including deficits in memory poorer motor performance

Food additives • Artificial or synthetic food colors and additives are ubiquitous in the food supply

•

Artificial food colorings such as sunset yellow, tartrazine, carmoisine and ponceau, as well as the preservative sodium benzoate, can cause conduct and hyperactivity disorders

Storage

Water Contamination by Pharmaceuticals and (active) Metabolits From Flu(sh) to Fish and Humans Tamiflu

• Oral contraceptives • Antidepressive agents incl. SSRI • Antibiotics • Soaps (antibacterial or not) • Insect repellants • Shampoos and Cosmetics • etc.

Br J Psychiatry. 2010 Feb;196(2):

CNN March 2008

Gitte Petersen 2009