Module 2: Toxin Exposure Among Children

Introduction: Toxic Chemicals

Chemicals surround us. Both natural and synthetic chemicals are used as pesticides, made into fibers for clothing, synthesized into medicines, and manipulated to build furniture, technological devices, and more. Chemicals, both natural and synthetic, have the potential to cause disease. Adverse health effects occur when toxic pollution is inhaled or ingested. While toxins threaten everyone’s health, infants and children are especially sensitive to toxins. This is because children are more exposed to chemicals (pound-by-pound), their organs are still developing, and their bodies are less able to detoxify. Children are also more vulnerable to toxins because they lack a fully developed blood-brain barrier, the structure in the central nervous system that prevents the passage of chemicals between the bloodstream and the neural tissue. Children today are exposed to an ever-increasing number of chemicals, many of which have not been tested for their possible toxicity. Thus, we must be especially careful to shield children from these environmental toxins.

Examples of Toxins

Heavy Metals

Heavy metals are elements with high atomic masses. Heavy metals with no known benefit for human physiology are considered "toxic metals" and include lead, mercury, and cadmium. Other heavy metals are necessary for life, including zinc, cobalt (found in vitamin B-12), and iron (found in hemoglobin). Furthermore, trace elements, such as copper, manganese, selenium, chromium, and molybdenum, are important to the human diet.(1)

Arsenic

Arsenic is number one on the 2017 Priority List of Hazardous Substances created by the Agency for Toxic Substances and Disease Registry (ATSDR). The National Priorities List (NPL) ranks the substances most commonly found at sites on the NPL, most of which are in America.(2) Arsenic is an element found naturally in soil, and often combines with other elements to form inorganic arsenic compounds. While it is well known for its use as a poison, arsenic is also used in wood preservatives, pesticides, and semiconductors. Background exposure to arsenic in air is typically less than 0.1 micrograms per cubic meter (µg/m3) and in drinking water is typically less than 5µg/L; people exposed to arsenic in contaminated drinking water or workplace air are exposed to higher levels of arsenic. Studies in the 1960s found that inorganic arsenic is a human carcinogen; since the U.S. Safe Drinking Water Act of 1975, nearly all pesticides based in inorganic arsenic compounds have been banned or voluntarily removed from the market. High and prolonged workplace exposure to inhaled arsenic has been associated with an increase in lung cancer, and some studies have suggested that workplace exposure to arsenic may increase the risk of skin, stomach, and kidney cancers, as well as leukemias and lymphomas.(3)

Arsenic poisoning in drinking water threatens the health of people globally. Some of the most serious cases of arsenic-contaminated groundwater have been found in aquifers in Asia (in Bangladesh, China, India, and Nepal) and South America (Argentina and Mexico). Ingestion of 70-180 mg of inorganic arsenic can cause death. Other acute effects of arsenic ingestion include difficulty breathing and swallowing, intestinal pain, vomiting, diarrhea, muscle cramps, and severe thirst. Symptoms of chronic arsenic poisoning, often due to drinking contaminated water, include garlic breath, extreme perspiration, muscle tenderness, changes in skin pigmentation, anemia, reduced sensation in the extremities, and peripheral vascular disease. Studies of people with high levels of arsenic in drinking water in Southeast Asia and South America have found higher risks of bladder, kidney, lung, skin, colon, prostate, and liver cancer. (4) Inorganic arsenic is a human carcinogen, according to the Department of Health and Human Safety (DHHS), the Environmental Protection Agency (EPA), and the International Agency for Research on Cancer (IARC);(5) In addition, Therefore, the WHO and EPA set current limits for arsenic in drinking water at 0.01 parts per million (ppm) and the Occupational Safety and Health Administration (OSHA) limits arsenic exposure in workplace air at 10 micrograms per cubic meter of air (10 μg/m³) for 8 hour shifts and 40 hour work weeks.(6)

Arsenic poisoning in drinking water in Bangladesh and West Bengal, India, is considered by some to be the worst mass poisoning in history.(7) Millions of wells were dug throughout Bangladesh and West Bengal in the 1960s and 1970s, but they were not tested for metal impurities until after they were discovered to be contaminated with arsenic. As a result, around 75 million people in affected regions of Bangladesh and India have been exposed to arsenic-contaminated water, and 200,000 to 270,000 deaths due to arsenic-induced cancer are expected in the future. A random survey conducted in 2001 of 3,208 groundwater samples in India and Bangladesh from shallow aquifers (less than 150 meters deep) found that 46% of the samples contained more than 10 μg/L of arsenic.(8) Efforts to reduce the level of contamination are hampered by the poverty of most Bangladeshis (annual per capita income of $1466) and of the government’s lack of resources. Furthermore, exactly how arsenic leaches into the water is not clear, making the problem more difficult to solve. For now, the best approach is to treat contaminated groundwater after it is drawn (which is too expensive for most people in West Bengal, India and Bangladesh) or to let water sit out for a while so that inorganic arsenic can be converted into less harmful organic arsenic.

Lead

Lead is second on the 2017 ATSDR Priority List of Hazardous Substances. Lead is a naturally occurring metal found in the Earth’s crust. In the past, lead has been used in the manufacture of gasoline, paints, ceramics, caulking, and solder pipe, but is no longer used to make these materials due to lead’s harmful health effects. In fact, federal and state regulatory standards have reduced the amount of lead in the air, drinking water, soil, consumer products, food, and in workplaces. (9) Because of these regulations, levels of lead in the blood of American children have dropped by 86% since the late 1970s from a median level of 15 µg/dL in 1976 (before regulations were passed and enforced) to a median level of 1.9 µg/dL in 1999. (10) However, lead is still used today in the manufacture of many products, including batteries, ammunition, metal pipes, and devices to shield X-rays.(11)

Although lead has many useful applications, it is known to cause health complications that affect almost all human organs. These complications include impaired intellect, memory loss, nerve disorders, infertility, mood swings, and problems with the cardiovascular, skeletal, kidney, and renal systems in adults. Lead can enter the body through ingestion or inhalation. Adults must be exposed to much more lead (compared to children) in order to suffer sustained health consequences. Most adults who suffering from lead poisoning are exposed to lead at work, especially in occupations related to welding, renovating, manufacturing car batteries, and maintaining bridges and water towers.(12) Children are most often exposed to lead in the form of dust and chips from deteriorating lead paint on the interior surfaces of older homes (built before lead paint was banned).

Children are most vulnerable to lead poisoning. In fact, two-year olds exposed to lead have the highest blood level concentration of lead, partly because they place many objects and toys, some laden with lead, in their mouths. Children with blood-lead concentrations greater than 10 micrograms per deciliter (µg/dL), or one millionth of a gram of lead in about half a cup of blood, have excess lead exposure. Recent studies, however, have shown that children with blood-lead concentrations of even less than 10 µg/dL experience adverse health effects.(13) Lead poisoning has been shown to cause cognitive impairment (decreased IQ) in children globally.(14) A study that analyzed the association between blood-lead concentrations and IQ in 172 children found that each increase of 10 µg/dL in the lifetime average blood-lead concentration was correlated with a 4.6 point decrease in IQ. In a subsample of children with maximal lead concentrations below 10µg/dL, a given change in lead concentration caused an even greater change in IQ.(15) Lead exposure has also been found to be associated with behavioral problems in 5- to 7-year-old children who were first exposed to dangerous levels of lead when they were 1-2 years old.(16) Children exposed to lead poisoning scored worse on a behavior test for opposition, hyperactivity, and attention deficit hyperactivity disorder (ADHD) than did their peers.

When the city of Flint, Michigan, under state-appointed emergency management, changed its water supply from Lake Huron to the Flint River in 2014, residents almost immediately began to complain about changes in color, taste, and odor. The water from the Flint River was highly corrosive and when it traveled through lead pipes to reach the residents of Flint, the lead concentration in the drinking water began to rise. Between 2013 and 2015, the incidence of blood lead concentrations above the safe level of 5 µg/dL in children living in Flint rose from 2.4% to 4.9% and was as high as 10.6% in neighborhoods that were most impacted. (17)

Mercury

Mercury is third on the 2017 ATSDR Priority List of Hazardous Substances. Elemental mercury is found naturally as an odorless, shiny liquid metal. Toxic mercury vapors can be released naturally (from volcanic eruptions and from the earth’s crust) or synthetically (from waste incineration, coal combustion in power plants, automobile emissions, and disposal of industrial waste). Mercury has been used to make thermometers, barometers, and fluorescent light bulbs. Mercury released into the air settles into water or on land, where it deposits and is converted (by microorganisms) into methylmercury, a highly toxic form of mercury that builds up in fish. (18) Therefore, people can be exposed to mercury by ingesting fish that contain mercury, inhaling mercury vapors, or touching mercury.

Mercury exposure can damage the brain, heart, kidney, lungs, and immune system. There are three different chemical forms of mercury: elemental mercury, organic mercury (primarily methylmercury), and inorganic mercury compounds, each of which causes different health effects. Elemental mercury, usually inhaled as vapors and found in thermometers, can cause mood swings, irritability, nervousness, insomnia, headaches, muscle twitching/tremors, and decreased cognitive functioning. Organic mercury, or mercury covalently bound to carbon, impairs neurological development in fetuses, infants, and children, because methylmercury can pass from mother to fetus through the placenta. Inorganic mercury, or mercury bound to inorganic compounds, often causes skin rashes, inflammation, muscle weakness, mental disturbances such as mood swings and memory loss, impairment of coordinated movements, and numbness in hands, feet, and sometimes the mouth. (19)(20)

Many people are concerned with mercury levels in fish. In 1997, the Environmental Working Group (EWG) found that fish from over 1,660 U.S. waterways contained too much mercury to be safe for consumption. Soon after, the EPA confirmed that more than 1.6 million women and children were at risk of mercury contamination from fish. In 2004, the EPA and the Food and Drug Administration (FDA) issued warnings limiting fish consumption during pregnancy to 12 ounces per week. The EPA and FDA recommendations targeted pregnant women because fetuses are especially vulnerable to mercury poisoning. Some fish contain dangerous levels of mercury for all people. All people should avoid eating the four types of fish containing the highest levels of methylmercury: king mackerel, marlin, orange roughy, shark, swordfish, tilefish, and big eye tuna.(21)

The disaster in Minamata Bay, Japan, is an example of a mercury outbreak. In 1908, the Chisso Corporation opened up a chemical factory in Minamata. The waste products from the plant were released into Minamata Bay. In 1925, the Chisso Corporation continued dumping untreated waste (containing methylmercury) into the bay, which damaged fisheries, and paid the fishermen for their losses. Not until the mid-1950s did people realize that some of the local residents had developed a “strange disease,” now referred to as Minamata disease. Minimata disease is a neurological syndrome caused by sever mercury poisoning. Symptoms of Minimata disease include ataxia, numbness in feet and hands, muscle weakness, narrowing of the field of vision and damage to hearing and speech. In extreme cases Minimata disease may lead to paralysis, coma, and death. As of 2001, 2265 victims had been officially recognized and by 2004 the Chisso Corporation had paid $86 million in compensation to victims and their survivors.(22)

“Developmental Delay in Cognitive Function for Each 10-Fold Increase in Prenatal Exposure to Mercury”(23)

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Carcinogens

Carcinogens are substances that can lead to cancer. Some carcinogens cause cancer by directly creating mutations in the DNA; others disrupt cell growth, thereby allowing some cells to grow uncontrollably. There are many known carcinogens that affect human health, including acetaldehyde, aflatoxins, asbestos, benzene, formaldehyde, hepatitis viruses, ionizing radiation, plutonium, radionuclides, radon, tobacco, and ultraviolet radiation.

Asbestos

Asbestos is the name given to six minerals that occur naturally as bundles of fibers that can be mined and then separated into thin, durable threads. These fibers are resistant to heat, chemicals, and fire, and do not conduct electricity. Therefore, asbestos fibers are commonly used for a variety of manufactured goods, including roofing shingles, ceiling and floor tiles, paper and cement products, textiles, and coatings. Asbestos minerals are classified into two major groups: serpentine asbestos (which have long, curly fibers that can be woven) and amphibole asbestos (which have straight, needle-like fibers that are more brittle and less able to be woven).(24)

Asbestos is has been classified as a known human carginogen, and is a health hazard when inhaled. When products containing asbestos are disturbed, tiny asbestos fibers are released into the air. Once inhaled, these tiny fibers may remain trapped in the lungs for a long time, scarring and inflaming the tissues, thereby disrupting breathing and causing long-term health problems.(25) Diseases from asbestos exposure take a long time to develop; cases of lung cancer or asbestosis may be diagnosed 15 years after a person’s initial exposure to asbestos. The three major health effects of asbestos exposure are:

  1. Asbestosis: a progressive, non-cancerous disease of the lungs. Asbestos fibers scar the respiratory tissues, making it more difficult for oxygen to enter the bloodstream. Symptoms include shortness of breath and a dry, crackling sound when inhaling. There are no effective treatments for asbestosis.(26)
  2. Lung cancer: a malignant tumor that invades and then obstructs the air passages in the lungs. Symptoms of lung cancer include coughing, difficulty breathing, shortness of breath, persistent chest pains, hoarseness, and anemia. People working in the milling, asbestos manufacturing, and mining industries have a higher risk of developing lung cancer than do people in other industries.(27)
  3. Mesothelioma: a rare form of cancer found in the membrane (thin lining) of the lung, chest, abdomen, and heart. Most mesotheliomas have been linked to asbestos exposure.(28)

Endocrine Disruptors

An endocrine disrupting compound is defined by the EPA as “an exogenous agent that interferes with synthesis, secretion, transport, metabolism, binding action, or elimination of natural blood-borne hormones that are present in the body and are responsible for homeostasis, reproduction, and developmental process.”(29) In other words, endocrine disruptors interfere with the functions and hormones of the innate endocrine system. Research has found that many endocrine disruptors are associated with early onset of puberty. Some synthetic endocrine disruptors include polychlorinated biphenyls (PCBs), plastics (bisphenol A), plasticizers (phthalates), pesticides (methoxychlor and DDT), fungicides (vinclozolin), and pharmaceutical agents (diethylstilbestrol). Some natural endocrine disruptors found in human and animal food include phytoestrogens (also known as dietary estrogen), such as genistein and coumestrol (found in soybeans, alfalfa, legumes, brussels sprouts, and spinach).(30)

Bisphenol A (BPA)

Bisphenol A is a synthetic estrogen used in plastics manufacturing to harden polycarbonate plastics and epoxy resin. Polycarbonate plastics are used in food and drink packaging (water and baby bottles), compact discs, eyeglasses, computer and cell phone cases, impact-resistant safety equipment, and medical devices. Epoxy resins are used to coat metal products such as food cans, bottle tops, and water pipes.(31)

BPA enters the body primarily through ingestion. BPA leaches from the epoxy can linings into canned foods. The degree to which BPA seeps from polycarbonate bottles into food and beverages depends on the temperature of the liquid or food, with more leaching occurring at higher temperatures. A 2003-2004 CDC study that found detectable levels of BPA in 93% of 2,517 urine samples of a random sampling of people over six years old.(32)

In 2008, the National Toxicology Program at the Department of Health & Human Services (NTP) and the FDA concluded that current low levels of human exposure to BPA are safe in adults, but they were concerned about the potential health effects of BPA on the brain, behavior, and prostate glands of fetuses, infants, and children.(33) As of 2018, the FDA determined that the BOA was safe for the currently approved food containers and packages. Studies conducted by the FDA’s National Center for Toxicological Research (NCTR) have found that low-dose exposure to BPA has no effect on human health.(34)

Phthalates

Phthalates are a group of chemicals invented in the 1930s. Phthalates are used as plasticizers to soften and increase the flexibility of plastics and make them more difficult to break. Phthalates are used in vinyl flooring, garden hoses, children’s inflatable toys, cosmetics including perfume, hair spray, soap, shampoo, nail polish, and skin moisturizers, detergents, and plastic clothes. People are exposed to phthalates when eating and drinking food packaged in phthalate-coated plastic, and to a lesser extent when breathing in air that is contaminiated with phthalate dust or vapors.(35) Children face an additional risk of exposure to phthalates due to their hand-to-mouth behaviors and from chewing on soft vinyl toys and other objects containing phthalates.

A study by the CDC found measurable levels of phthalate metabolites in the general U.S. population which suggests that phthalate exposure is widespread.(36)

Exposure to phthalates may be detrimental to human health. High levels of phthalates have been linked to decreased sperm motility and concentration, damaged sperm DNA, and alterations in hormone levels in adult men. In fact, a study in 2005 found significant differences in the reproductive systems of baby boys whose mothers had high phthalate levels during pregnancy. Studies also suggest that phthalates may alter thyroid hormone levels and increase insulin resistance in adult men.(37) The biological mechanisms behind the effects of phthalates are still being explored.

In 2008, Congress passed the Consumer Project Safety Improvement Act of 2008 which permanently prohibited manufacturers from producing children’s toys or child care items that contained concentrations of more than 0.1% of three types of phthalates. This interim rule was made permanent as of April 25, 2018.(38)

Methyl isocyanate

Methyl isocyanate is a highly toxic, flammable, colorless liquid. It is used in the production of rubbers, adhesives, and pesticides. Methyl isocyanate gas was present in the gas leak from a pesticide plant in Bhopal, India, on the night of December 2, 1984.(39) The 40 tons of leaked methyl isocynate gas killed over 3,800 people instantly and caused premature death for thousands more.(40) The Bhopal disaster illustrated the negative impact of rapid industrialization in a nation where safety regulations were not keeping pace with industrialization. Public health infrastructure in Bhopal in 1984 was very weak; poor-quality tap water was accessible for only a few hours of the day, human waste was dumped into nearby lakes (a source of drinking water), the four hospitals in the city were all short on staff and beds, and there was no established mass casualty emergency response system.(41) Following the events of the Bhopal disaster, environmental awareness and activism in India increased significantly. For example, the Environmental Protection Act was passed in 1986, creating the Ministry of Environment and Forests (MoEF) to administer and enforce environmental policies.(42)

Environmental Teratogenic Agents

Teratogenic agents, or teratogens, are toxins that cause abnormal development, leading to birth defects. Of the 3-5% of American children born per year with birth defects, only 2-3% of them are considered to have teratogen-induced malformations.(43) Fetuses are most vulnerable to toxins during organogenesis, when the organs begin to develop (approximately 3 weeks post-conception). The type and severity of the birth defect are related to the duration of exposure and the specific teratogen. Teratogenic agents are classified as genetic or environmental. Genetic agents are changes in the genetic material of the fetus that are either inherited or newly acquired. Common environmental teratogenic agents include radiation, metals (such as methylmercury), thalidomide , ethanol (alcohol), nicotine, and cocaine.(44) These toxins harm the health of exposed mothers, as well as individuals who are prenatally exposed to these toxins.

Ethanol/Alcohol

Alcohol consumption causes approximately 88,000 deaths and 2.5 million years of potential life lost (YPLL) per year in America.(45) For adults, immediate health risks of alcohol consumption include unintentional injuries (traffic accidents, falls), domestic violence , and miscarriage and stillbirth (among pregnant women). Long-term health effects include neurological problems (dementia, stroke, neuropathy), cardiovascular problems (hypertension), psychiatric problems (depression, anxiety), cancer (of the mouth, esophagus, colon, and breast), and liver diseases.(46)

Developing fetuses are especially vulnerable to alcohol exposure. Excessive drinking during pregnancy increases a woman’s risk of miscarriage, stillbirth, and premature delivery. Fetal Alcohol Spectrum Disorders (FASD), the most serious of which is Fetal Alcohol Syndrome (FAS) is also caused by excessive alcohol consumption during pregnancy. FAS causes mental retardation and birth defects.(47) Studies show that prenatal exposure to alcohol causes children to suffer significant cognitive defects and behavioral problems due to the alcohol-related changes in brain structure (specifically, changes in the basal ganglia, corpus callosum, cerebellum, and hippocampus).(48) Children prenatally exposed to lower amounts of alcohol and children with FAS experience learning and memory deficits, behavioral problems (drug and alcohol abuse), hyperactivity, impulsivity, decreased sociability, and poor communication skills.(49)

Common Symptoms of Fetal Alcohol Syndrome(50)
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Nicotine

Nicotine, an ingredient found in tobacco plants and used to make cigarettes and other tobacco products, is a highly toxic and addictive drug. Only 60 mg of nicotine is lethal to an adult, and smokers generally receive 1 mg of nicotine per cigarette smoked. Acute effects of nicotine poisoning for adults include nausea, vomiting, salivation, diarrhea, dizziness, confusion, and weakness. Higher levels of exposure to nicotine causes decreased blood pressure, difficulty breathing, irregular pulse, convulsions, respiratory failure, and death.(51)

Nicotine also affects the developing fetus; chronic prenatal nicotine exposure leads to reduced infant birth weight, attention deficit disorders, and other cognitive problems in children.(52) Studies using animal models found birth defects in rats exposed to nicotine, including decreased birth weight, increased infant mortality, delayed sensorimotor development, higher levels of anxiety, and changes in learning and memory(53)(54). Recent studies have confirmed the teratogenic nature of prenatal tobacco exposure. Prenatal tobacco exposure affects speech processing, irritability, attention levels, ability to self-regulate, and response to novelty in infants.(55) 

Thalidomide

Thalidomide, a sedative drug, was first widely used in the 1950s to treat morning sickness among pregnant women. In 1961, thalidomide was withdrawn after it was shown to cause birth defects. Today, thalidomide is used to successfully treat a wide range of medical conditions including cancers such as multiple myeloma, leprosy, Crohn’s disease, HIV, and others.(56)

Women who take just one dose of thalidomide during pregnancy may give birth to a child with a birth defect. Thalidomide exposure during pregnancy may lead to malformation of craniofacial structures and extremities, malformation of the ear (leading to hearing loss), ocular anomalies (glaucoma, refractive error), facial nerve palsy, defects in the central nervous system, and mental retardation.(57) Thalidomide exposure in adults is associated with peripheral neuropathy, blood clots, drowsiness, seizures, rash, headache, weakness, weight changes, constipation, dry mouth, and swelling of the hands, ankles, feet, or lower legs.(58)

Children with Thalidomide-Related Birth Defects at a Swimming Pool(59)

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Footnotes

(1) Adefris, A, "Heavy Metal Toxicity." (2018). https://emedicine.medscape.com/article/814960-overview#a0101. Accessed on 31 July 2018.

(2) ATDSR. "The Priority List of Hazardous Substances That Will Be the Subject of Toxicological Profiles." www.atsdr.cdc.gov. Accessed on 31 July 2018.

(3) American Cancer Society. "Arsenic and Cancer Risk." https://www.cancer.org/cancer/cancer-causes/arsenic.html. Accessed on 31 July 2018.

(4) Ibid.

(5) USDHHS, ATSDR. "Toxicological Profile for Arsenic." Aug. 2007. https://www.atsdr.cdc.gov/toxprofiles/tp2.pdf. Accessed on 31 July 2018.

(6) Ibid.

(7) Chowdury, et al., "Groundwater Arsenic Contamination in Bangladesh and West Bengal, India." Environmental Health Perspectives, vol 208, no. 5 (May 2000). Arsenic Poisoning in Bangladesh." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1638054/pdf/envhper00306-0043.pdf. Accessed on 31 July 2018.

(8) Appelo T. "Arsenic in Groundwater: A World Problem." Utrecht, The Netherlands: Secretariat Netherlands National Committee, IAH, 2006. http://bigfiles.nhv.nu/files/Arsenic_in_Groundwater_A_World_Problem.pdf. Accessed on 31 July 2018.

(9) EPA. "Learn about Lead." https://www.epa.gov/lead/learn-about-lead. Accessed on 31 July 2018.

(10) American Academy of Pediatrics Committee on Environmental Health. "Lead exposure in children: Prevention, detection, and management." Pediatrics.2005; 116:1036–1046.

(11) ATSDR. "Toxic Substances Portal: Lead." https://www.atsdr.cdc.gov/substances/toxsubstance.asp?toxid=22. Accessed on 31 July 2018.

(12) NIEHS. "Lead and Your Health." https://www.niehs.nih.gov/health/materials/lead_and_your_health_508.pdf. Accessed on 31 July 2018.

(13) Ibid.

(14) Ibid.

(15) Canfield R, et al. "Intellectual impairment in children with blood lead concentrations below 10 micrograms per deciliter." N Engl J Med. 348.16 (2003): 1517-26.

(16) Chen, et al. "Lead exposure, IQ, and behavior in urban 5-to 7-year-olds: Does lead affect behavior only by lowering IQ?" Pediatrics 119.3 (2007): e650-e658.

(17) Hanna-Attisha, et al. "Elevated blood lead levels in children associated with the Flint drinking water crisis: a spatial analysis of risk and public health response." AJPH 106.2 (2016): 283-290.

(18) NIEHS. "Mercury." https://www.niehs.nih.gov/health/topics/agents/mercury/index.cfm. Accessed on 31 July 2018.

(19) Ibid.

(20) EPA. "Mercury." https://www.epa.gov/mercury. Accessed on 31 July 2018.

(21) "2017 EPA-FDA Advice about Eating Fish and Shellfish,”https://www.epa.gov/fish-tech/2017-epa-fda-advice-about-eating-fish-and-shellfish. Accessed on 6 July 2018.

(22)“Minimata Disease.”http://www.bu.edu/sustainability/minamata-disease/. Accessed on 1 August 2018.

(23) NIEHS. "Developmental Delay in Cognitive Function for Each 10-Fold Increase in Prenatal Exposure to Mercury." Digital image. www.niehs.nih.gov. Accessed on 1 June 2012.

(24) National Cancer Institute. "Asbestos Exposure and Cancer Risk." https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/asbestos/asbestos-fact-sheet. Accessed on 1 August 2018. See also, EPA. "Asbestos." https://www.epa.gov/asbestos. Accessed on 1 August 2018.

(25) Ibid.

(26) Ibid.

(27) Ibid.

(28) Ibid.

(29) Diamanti-Kandarakis E, et al. " Endocrine-Disrupting Chemicals:  An Endocrine Society Scientific Statement." Endocrine Reviews. 30.4 (2009): 293-342

(30) Ibid.

(31) NIEHS. "Bisphenol A (BPA)." August 2010. https://www.niehs.nih.gov/health/materials/bisphenol_a_bpa_508.pdf. Accessed on 1 August 2018. 

(32) Ibid.

(33) FDA. "Questions & Anbswer on Bisphenol A (BPA) Use in Food Contact Applications.”https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm355155.htm. Accessed on 1 August 2018.

(34) Ibid.

(35) CDC National Biomonitoring Program. “Phthalates Factsheet.”https://www.cdc.gov/biomonitoring/Phthalates_FactSheet.html. Accessed on 1 August 2018.

(36) Ibid.

(37)“Report to the U.S. Consumer Product Safety Commission by the Chronic Hazard Advisory Panel on Phthalates and Phthalate Alternatives.” July 2014. https://www.cpsc.gov/PageFiles/169902/CHAP-REPORT-With-Appendices.pdf. Accessed on 1 August 2018.

(38) U.S. Consumer Product Safety Commission. “Phthalates.”https://www.cpsc.gov/Business--Manufacturing/Business-Education/Business-Guidance/Phthalates-Information. Accessed on 1 August 2018.

(39) Broughton E. "The Bhopal disaster and its aftermath: A review." Environmental Health. 4.1 (2005): 6.

(40) Ibid.

(41) Ibid.

(42) Ibid.

(43) Gilbert S. "A Small Dose of Toxicology: The Health Effects of Common Chemicals." 2nd ed. Seattle: Healthy World, 2012. http://aulanni.lecture.ub.ac.id/files/2012/01/Toxicology_0415311683.pdf . Accessed on 1 August 2018.

(44) Ibid.

(45) CDC. "Fact Sheets - Alcohol Use and Your Health." https://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm. Accessed on 6 July 2018.

(46) CDC. “Fact Sheets – Excessive Alcohol Use and Risks to Women’s Health,”https://www.cdc.gov/alcohol/fact-sheets/womens-health.htm. Accessed on 6 July 2018.

(47) Ibid.

(48) Mattson S., Schoenfeld A., & Riley, E. "Teratogenic Effects of Alcohol on Brain and Behavior." National Institute on Alcohol Abuse and Alcoholism (NIAAA). https://pubs.niaaa.nih.gov/publications/arh25-3/185-191.htm. Accessed on 1 August 2018.

(49) Ibid.

(50)"Fetal Alcohol Syndrome Symptoms Chart Picture." Digital image. https://syndromespedia.com/fetal-alcohol-syndrome-symptoms-pictures-treatment-effects.html. Accessed on 1 August 2018.

(51) Gilbert S. "A Small Dose of Toxicology: The Health Effects of Common Chemicals." 2nd ed. Seattle: Healthy World, 2012. http://aulanni.lecture.ub.ac.id/files/2012/01/Toxicology_0415311683.pdf . Accessed on 1 August 2018.

(52) Ibid.

(53) Schneider T, Ilott N, Brolese G, Bizarro L, Asherson P, & Stolerman I. "Prenatal exposure to nicotine impairs performance of the 5-choice serial reaction time task in adult rats." Neuropsychopharmacology. 2011 Apr; 36(5):1114-25.

(54) Vaglenova J, et al. "Long-lasting teratogenic effects of nicotine on cognition: Gender specificity and role of AMPA receptor function." Neurobiology of Learning and Memory. 2008; 90(3):527–536.

(55) Cornelius M, & Day N. "Developmental consequences of prenatal tobacco exposure." Curr. Opin. Neurol. 2009; 22:121–125.

(56) Vargesson N. "Thalidomide‐induced teratogenesis: History and mechanisms." Birth Defects Research Part C: Embryo Today: Reviews. 105.2 (2015): 140-156. https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdrc.21096. Accessed on 1 August 2018.

(57) Miller M, & Strömland K. "Teratogen update: thalidomide: a review, with a focus on ocular findings and new potential uses." Teratology. 1999 Nov; 60(5): 306–321. 

(58) Medline Plus. "Thalidomide." U.S. National Library of Medicine. https://medlineplus.gov/druginfo/meds/a699032.html. Accessed on 1 August 2018.

(59)“The First Appearance of Thalidomide." Digital image. http://www.chm.bris.ac.uk/motm/thalidomide/first.html. Accessed on 1 August 2018.