Pediatric environmental health

Pediatric environmental health

Pediatric Environmental Health Lynnette J. Mazur, MD, MPH Introduction: Why Children are More Vulnerable ediatric environmental health is the diagnos...

187KB Sizes 1 Downloads 76 Views

Pediatric Environmental Health Lynnette J. Mazur, MD, MPH

Introduction: Why Children are More Vulnerable ediatric environmental health is the diagnosis, treatment, and prevention of illness caused by preconception, prenatal, perinatal, and pediatric exposures to environmental hazards; and the creation of healthy environments for children. Exposure to pollutants in air, food, and water as well as chemicals in the environment can be potentially helpful or harmful. The toxicity of the vast majority of the 85,000 chemicals manufactured in the United States is unknown. This coupled with increases in the prevalence of asthma, attention deficit disorder, birth defects, cancer, and developmental delay have lead many to question whether there is a causal relation. Response to environmental toxins varies according to a person’s physical, biological, and behavioral characteristics.1 Biological or physiologic characteristics determine how the body absorbs, distributes, and metabolizes environmental exposures and behavior varies according to a person’s developmental stage and social milieu. Additionally, specific responses to acute and chronic exposures differ from person to person. Physical exposures vary with age and development. Because they are growing, children drink more water, eat more food, and breathe more air per body size and surface area than adults. Because of their higher metabolic rate, children consume more oxygen than adults and may have more adverse effects to air pollutants. Infants in the first 6 months of life drink 7 times as much water per pound as does the average adult. Children ages 1 to 5 years of age eat 3 to 4 times more food per pound than the average adult. In

P

From the University of Texas, Memorial-Hermann Children’s Hospital, Houston, TX. Curr Probl Pediatr Adolesc Health Care 2003;33:1-25. Copyright © 2003 by Mosby, Inc. All rights reserved. 1538-5442/2003 $30.00 ⫹ 0 doi:10.1067/mps.2003.1

6

addition, children have unique food preferences. For example, the average 1-year-old drinks 21 times more apple juice and 11 times more grape juice and eats more grapes, bananas, pears, carrots, and broccoli than does the average adult.2 Biologically, a child’s immature metabolic pathways less readily detoxify and excrete certain toxins. Additionally, nonambulatory children are not able to remove themselves from potentially harmful locations. Behaviorally, children live and play closer to the ground, which increases their exposure. Their handto-mouth behavior increases their risk as well. With more years of life before them, early environmental exposures may permit the development of chronic diseases.

Absorption Absorption can occur through the placenta, skin, airways, and gastrointestinal tract. Transplacental absorption can have deleterious effects for the developing child. Lipophilic compounds such as polycyclic aromatic hydrocarbons (found in cigarette smoke), methyl mercury, and ethanol easily cross the placental barrier. A case-control study of children whose mothers worked with organic solvents during pregnancy showed that the children were more likely to have visual problems, including color blindness.3 Newborn infants are at increased risk from dermal absorption because the protective keratin layer develops only 3 to 5 days after birth. Cases of hypothyroidism from absorption of the iodine in Betadine solutions, neurotoxicity from hexachlorophene, and hyperbilirubinemia from phenolic disinfectants have been reported.4 – 6 In France, 36 children were poisoned and died from an overdose of baby powder that contained hexachlorophene.7 An additional factor in dermal absorption is the larger surface-to-body mass ratio of newborns infants compared with older children and adults. The newborn infant has a 3-times-larger surface-to-mass

Curr Probl Pediatr Adolesc Health Care, January 2003

ratio, and the child has a 2-times-larger surface-tomass ratio than the adult. Thus, for the surface area of skin covered with a chemical, a newborn may absorb up to 3 times and an older child up to 2 times the amount absorbed by an adult.8 Application of lindane, which is commonly used for the treatment of scabies, and of insect repellants have been reported to cause seizures.9,10 There is an extended period of postnatal lung development in children. Proliferation of pulmonary alveoli and capillaries continues for 5 to 8 years. Early lung development is especially important in determining long-term respiratory health.11 Studies have shown reduced pulmonary functions in infants exposed to environmental tobacco smoke in utero.12,13 Infants and children have higher metabolic and respiratory rates and have increased susceptibility to other noxious gases. One report showed differences in carbon monoxide (CO) kinetics between a mother and her unborn child. After an acute exposure to CO, the infant’s carboxyhemoglobin (COHb) level was 61% compared with the mother’s level of 7%.14 Fetal tissues are at greater risk from hypoxia caused by CO because a higher COHb equilibrium is achieved, COHb elimination is delayed, and fetal hemoglobin has a more accentuated left shift than does adult hemoglobin. Differences in the gastrointestinal tract also exist. Infants have lower gastric acid secretion than adults. When acid levels are low, bacterial overgrowth occurs in the intestines and chemical absorption is altered. Infants who drink well water contaminated with nitrates are at risk of methemoglobinemia when intestinal bacteria convert nitrates to nitrites.15 Lead is also absorbed to a greater extent in the immature intestine; an adult absorbs 10% of ingested lead, whereas a child can absorb up to 50%.16

Distribution The distribution of chemicals within the body varies with age. A tragic example was the epidemic of bread contamination in Iraq in the 1970s. The source of poisoning was methyl mercury–treated seed grain that was used to make bread. The pregnant mothers had reversible mild symptoms, but the infants were severely affected with developmental delay, seizures, blindness, and deafness.17,18

Metabolism Metabolism of a chemical may result in either activation or deactivation. Although differences be-

Curr Probl Pediatr Adolesc Health Care, January 2003

tween metabolism in children and adults may result in increased toxicity, they occasionally are protective. Infants born to women with dangerously high blood acetaminophen levels have similar acetaminophen levels but do not have liver damage because their livers are immature and unable to break down acetaminophen into harmful metabolites.19

Air Indoor Indoor air pollutants include gases, biological materials, heavy metals, and fibers. Sources of indoor pollutants include tobacco smoke, heating and cooking fuels, animals, insects and arthropods, and outgassing of vapors. Absorption of air contaminants can occur through inhalation or dermal contact. Respiratory and nonrespiratory adverse events result. Asbestos. Asbestos is a fibrous mineral composed of silicate combined in various proportions with magnesium, iron, calcium, aluminum, sodium, and trace elements. Chrysotile, silicate-containing magnesium, accounts for over ⬎90% of the asbestos in use. Because it does not burn, dissolve, evaporate, or react with other chemicals, it has been widely used in many commercial and domestic products. Asbestos can also be found in drinking water that may contain asbestos from natural land sources, discarded mine debris, or asbestos-containing cement pipes. The Environmental Protection Agency (EPA)-proposed maximum contaminant level for asbestos in water is 7 million fibers per liter. In the past, asbestosis was an occupational hazard in miners and in workers engaged in product manufacturing, and in construction and shipyard workers. Today, most exposures occurs during repair, renovation, removal, or maintenance of asbestos that is present in older buildings. When disturbed, asbestos can be inhaled into the respiratory tract, the primary target. Clinical manifestations typically appear 10 to 30 years after exposure. The main risks are lung cancer and malignant mesothelioma. Because there are no symptoms with acute exposure, screening is not feasible. Once diagnosed, asbestosis is irreversible. Patients with mesothelioma seldom live longer than 12 to 18 months after the diagnosis. There is no efficacious treatment.20,21 In 1980 (the last time that national statistics were compiled) the EPA estimated that more than 8500

7

schools nationwide contained deteriorated asbestos, and that approximately 3 million students (and also more than 250,000 teachers and school personnel) were at risk of exposure.22 To prevent asbestos exposure in schools, the EPA proposes: (1) medical screening of children who have been exposed to asbestos is not recommended because exposure does not produce detectable radiographic changes in the lungs for 5 to 30 years after exposure; (2) because no worthwhile medical screening exists, all efforts should focus on prevention; and (3) visual inspection of walls and ceilings is the key to prevention. Asbestos hazard legislation mandates that every surface of every school must be inspected for the presence of asbestos every 3 years by a trained and certified inspector. In the event that asbestos is detected, abatement, containment, or watchful waiting are possible options. Abatement is mandatory when deteriorating asbestos is accessible to children. Otherwise, containment of asbestos is the most common approach. Watchful waiting is permissible only when no potential exposure exists. Biologic materials. Sources of biologic pollutants include allergens, bacteria, and molds. These agents may cause disease through infection, hypersensitivity, or toxicosis. Allergens such as dust mites,23 cockroaches,24 cats,25 and molds26 may cause as well as exacerbate asthma. Measures for controlling dust mite allergens and even reversing bronchial hyperreactivity include covering pillows and mattresses with plastic materials, eliminating feather pillows and comforters, washing bedding frequently in hot water, removing carpeting, vacuum-cleaning carpets and upholstered furniture, and using acarides.27,28 Also, lowering humidity to ⬍50% can result in a 10-fold reduction in mite concentrations.29 Measures for controlling cat exposure include removal of the pet from the household or weekly washings.30,31 Molds proliferate in areas of high relative humidity. Water reservoirs (humidifiers, dehumidifiers, and air conditioners) and water-damaged areas are havens for mold growth. Home dampness and school dampness have been associated with high respiratory morbidity and mortality rates in children with asthma.32–34 Toxin-producing molds such as Fusarium, Tricoderma, and Stachybotrys have been associated with skin rash and pulmonary hemorrhage35,36 and hemosiderosis.37 In 1994, the Centers for Disease Control and Prevention (CDC) performed a case-control study of the 10

8

infants in Cleveland, Ohio, who had acute pulmonary hemorrhage between January 1993 and December 1994. Results indicated that the acute pulmonary hemorrhage was associated with household water damage during the previous 6 months and with increased levels of airborne toxigenic fungi, including S atra in the home. Upon reanalysis of the original data, the CDC claims that the association should not be considered proven, and the underlying cause of the problem is unresolved. Although the odds ratio was lower after reanalysis, it still remained significant (odds ratio ⫽ 1.5; 95% CI, 1.1 to 2.5). The biological explanation is plausible; the toxins are protein synthesis inhibitors and can cause pulmonary capillary fragility. “Humidifier fever” has been related to exposure to amoebas, bacteria, and fungi found in humidifier reservoirs, air conditioners, and aquaria.38 The etiological factors are unknown, but bacterial endotoxins are suspected. Flu-like symptoms such as fever, headache, chills myalgia, and malaise occur a few hours after exposure and last for about 24 hours. Specific measures for controlling exposures to molds include cleaning water reservoirs, repairing leaks, and drying water-damaged areas. Carbon monoxide. Carbon monoxide is an odorless, colorless, tasteless gas. Anything that burns fuel (charcoal grills, hot water heaters, gas ranges, fireplaces, or motor vehicles) is a potential source. CO is the leading cause of poison-induced deaths in the United States.39 Because the affinity of CO for hemoglobin is approximately 250 times that of oxygen, it inhibits the transport, delivery, and utilization of oxygen, and less oxygen is delivered to tissues. Intoxication and death are due to hypoxia. Nonlethal exposures may cause flu-like symptoms such as headache, lethargy, nausea, syncope, or vomiting. Physical findings such as cherry-red mucous membranes and retinal hemorrhages occur late. To correctly diagnose a patient with vague flu-like symptoms, the health care provider should routinely ask about environmental exposures. The diagnosis is confirmed by direct measurement of the carboxyhemoglobin level (COHg). Pulse oximetry and arterial blood gases are unreliable; oximetry cannot differentiate oxyhemoglobin from COHg, and arterial oxygen tension (PaO2) is not affected by changes in hemoglobin saturation in a blood gas specimen. Because CO is endogenously produced in humans during metabolism of protoporphyrin to bilirubin in hemoglobin metabo-

Curr Probl Pediatr Adolesc Health Care, January 2003

lism, a nonsmoking individual may have a COHb saturation up to 1%. Exposure to cigarette smoke increases baseline COHg measurements up to 8%. Treatment of CO poisoning includes removal from the source and treatment with supplemental oxygen. The elimination half-life of COHb is approximately 4 hours in room air, 1 hour with supplemental oxygen, and 30 minutes with hyperbaric oxygen. However, as many as 40% of those treated have long-lasting neuropsychologic effects.40 Prevention of poisoning is possible with the careful maintenance of fuel-powered equipment and the use of CO detectors. Environmental tobacco smoke. It is well established that cigarette smoking is a major cause of death and disease. According to the US Department of Health and Human Services, tobacco use is responsible for more than 1 of every 6 deaths. The threat to health from tobacco use is not limited to the smoker. Others who are near a smoker are exposed to passive smoke. Environmental tobacco smoke (ETS) is composed of exhaled mainstream smoke, sidestream smoke emitted from the smoldering tobacco between puffs, contaminants emitted into the air during the puff, and contaminants that diffuse through the cigarette paper and mouth between puffs. More than 40% of children are exposed to ETS in their home, and almost 32% of 12th graders are current smokers (defined as having smoked within the past 30 days). Exposure increases a person’s risk of a multitude of illnesses. Table 1 lists the ABCs of tobacco exposure.41–92 Smoking cessation is the most effective means to reduce exposure to ETS. For parents who are not ready to quit, specific goals and time lines for reducing exposure should be discussed. Elimination of smoking in the home and in motor vehicles reduces but does not eliminate a child’s exposure but is a step in the right direction. A recent report by the National Cancer Institute (NCI) shows a decline in adolescent smoking rates over the past few years (http://cancercontrol.cancer.gov/tcrb/nci_monographs). The evidence indicates that prevention programs work when they address the full range of influences on youth tobacco use, such as tobacco-free policies, active parent and community involvement school-based programs, cessation services, and media to counter tobacco advertising. Data on the effect of price show that youth are more responsive to cigarette price increases than adults. A 10% increase in the price of cigarettes is estimated to reduce youth smoking by 5% or more. Despite this progress, there remains a need for more research and

Curr Probl Pediatr Adolesc Health Care, January 2003

TABLE 1. The ABCs of tobacco

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Asthma,41–45 attention deficit disorder46 Bone density,47 bronchiolotis,45 burns48 Cancer,49 cataracts,50 cholesterol,51 cleft lip/palate52 Dental disease,53 depression54,55 Ectopic pregnancy56 Failure to thrive, fetal tobacco syndrome,57 fire48 Gastroesophageal reflux,58 gingivitis,53 green tobacco sickness59 Halitosis,60 1HIV transmission,61 hyperlipidemia62 Inflammatory bowel disease,63 2IQ64 Jitteriness65 Kills (4 million deaths per year worldwide)66 Leukemia,67 lupus68 Macular degeneration,69 meningitis,70 breast milk2,71 myeloma67 Nicotine poisoning72 Obstructive sleep apnea,73 otitis media74,75 Placenta previa,76 platelet aggregation1,77 pneumonia,78 prematurity79 Quit80 Radiation81 Sinusitis,82 strabismus,83 sudden infant death84,85 Tonsillopharyngitis86 Upper respiratory tract infections87 VLDL188 Wheezing,89 wilms tumor49 eXercise-induced bronchospasm90 Yellow teeth91 Zero tolerance, ZZZs (disturbed sleep)92

for antismoking programs designed both to prevent children from starting to smoke and to help them quit if they have. There is a particular need for research among certain ages or racial/ethnic groups wherein which smoking trends have not decreased or, in some cases, continued to increase. Tobacco control programs at the NCI can be accessed at http://cancercontrol.cancer.gov.tcrb. Mercury. Mercury (Hg) occurs in three forms: inorganic elemental (Hg0, quicksilver), inorganic salts (mercurous Hg1⫹ and mercuric Hg2⫹), and organic. Elemental mercury is a silver-gray liquid that is used in batteries, dental amalgams, latex paints, sphygmomanometers, thermometers, and thermostat switches. The major source of atmospheric mercury is the off-gassing of mercury from soils and surface waters. Elevated levels have been reported in children whose parents work in a mercury-thermometer plant.93 Exposure has also occurred from interior latex paint.94,95 Vapor concentrations are also increased in persons with dental amalgams.96,97 However, a National Institutes of Health expert panel concluded that amalgam fillings pose no significant risk of side effects and

9

should not be replaced simply because they contain mercury.98 Because of mercury’s high vapor pressure, it is almost completely absorbed across the alveolar membrane when inhaled. Children are at increased risk because mercury vapor is heavier than air and settles to the floor. The major acute health effect is pulmonary toxicity. Symptoms include cough, dyspnea, chest pain, nausea, vomiting, fever, and a metallic taste in the mouth. Later, interstitial pneumonitis, necrotizing bronchiolitis, and pulmonary edema may develop. Conjunctivitis and an erythematous pruritic rash have also been reported. When chronic exposure to lower vapor concentration occurs, the nervous system and kidneys are key targets. Erethism is a central nervous system manifestation of mercury toxicity characterized by neuropsychiatric signs, including memory impairment, insomnia, emotional lability, and excessive shyness. The Mad Hatter in Alice in Wonderland may have exhibited this syndrome. Peripheral neuropathy begins as a tremor and may progress to sensory impairment (paresthesia). Renal effects include a proteinuria and or nephrotic syndrome. Acute tubular necrosis with resultant kidney failure may occur. Mercury can be measured in blood, urine, and hair. Blood measurements are preferred for acute exposures and urine measurements for chronic exposures. Treatment consists of removing the patient from the source and possible chelation therapy with either D-penicillamine or succimer (dimercaptosuccinate). Cleaning and chelation should be done in consultation with a local health department and a physician trained in toxicology. Primary preventive measures have included the removal of phenylmercury from interior paints in 1990 and exterior paints in 1992. Radon. Natural sources of ionizing radiation make up ⬎80% of all background radiation. Radon is the most common source, at 55%. Radon is a colorless, odorless, and tasteless gas derived from the radioactive decay of uranium. It enters buildings through cracks in the foundation, porous cinder blocks, and granite walls. Upon further decay, the isotopes emit ␣-radiation. The amount of radon emanating from the earth and concentrating in homes varies by region. Areas in the country that are likely to have homes with elevated radon levels are those with significant deposits of granite, uranium, shale, and phosphate. The EPA estimates that 6% of US homes

10

have radon levels that exceed 4 pCi/L (the background level of radon naturally found in outdoor air). Exposure produces no acute symptoms. The only established effect is lung cancer, which develops after a long latency period. Annually, the EPA estimates that 14,000 deaths from lung cancer are attributable to indoor radon and that 14% of all current cases of lung cancer are attributable to radon. The risk is 10 to 20 times greater in persons who smoke.99 Unfortunately, there are no reliable methods of testing for radon prior to construction. In 1988, the EPA and the Office of the Surgeon General recommended that all US homes below the third floor be tested for radon. Two measurement methods are available; the ␣-track detectors estimate exposure over a 3-month period of time and the charcoal canisters estimate exposure over a 4-day period. If levels exceed 4 pCi/L, repairs should be made. Quick control measures include increasing the ventilation by opening windows and increasing air movement with ceiling fans. More definitive measures include sealing the foundation, by subslab depressurization (creating negative pressure in the soil). The AAP Committee on Environmental Health states that because of the long latent period before disease develops, exposure to children is also a concern.100 Volatile organic compounds. Volatile organic compounds (VOCs) are chemicals that emit gases at room temperature. Examples include benzene, formaldehyde, styrene, xylene, and various chlorinated and brominated compounds. Building materials, household furnishings, and many personal items such as perfumes and hairsprays contain VOCs. Symptoms related to formaldehyde exposure range from burning and tingling in the eyes, nose, and throat to chest tightness and wheezing. Signs and symptoms related to exposure to other VOCs might include eye and upper respiratory irritation, rhinitis, nasal congestion, rash, pruritus, headache, nausea, vomiting, and dyspnea.101 Control and prevention measures include adequate ventilation and increased ventilation when using products known to emit VOCs, and not storing open containers of unused paint products in the house.

Outdoor Although outdoor air pollution has improved since the Clean Air Act was enacted in the United States in the 1960s, it is still an ever-present part of urban

Curr Probl Pediatr Adolesc Health Care, January 2003

living. Children are at increased risk of exposure because they spend more time outdoors than adults. They are also at increased risk for toxicity because of their smaller airways. Electromagnetic fields. Controversy continues about the health effects of electromagnetic fields. Epidemiological studies or meta-analyses are inconclusive. A study by the National Research Council on the relation between childhood leukemia and residential proximity to power lines concluded that living in homes classified as high wire-code is associated with a 1.5-fold excess of childhood leukemia.102 The National Cancer Institute performed a similar study and found no association between living near a power line and leukemia.103 Differences in the results could be due to the degree of heterogeneity between studies, especially with respect to methods of exposure assessment and choice of the respective cutoff relevant for an increase in cancer risk. Ozone. Ozone (O3) is a chemical variant of oxygen. In the upper atmosphere, it benefits us by preventing excessive heat reaching the earth and absorbing ultraviolet light. Its formation at ground level is unrelated to ozone in the upper atmosphere. As a constituent of smog, it is formed when VOCs and nitrogen oxides are exposed to sunlight. Because ozone requires sunlight for its formation, it is primarily a summer pollutant.104 Although primarily an outdoor pollutant, indoor concentrations can vary from 10% to 80% of outdoor levels, depending on the amount of air entering a building. Ozone is mainly a respiratory irritant, and its adverse effects are most notable in persons with respiratory illnesses. Ozone provokes both early-phase (within minutes) and late-phase (lasting days to weeks) bronchoconstriction in persons with asthma. It can potentiate bronchoconstriction with exposure to other pollutants such as sulphur dioxide. Other health effects can include nausea, headache, malaise, and a decreased ability to perform exercise. The National Ambient Air Quality Standards require that regulatory areas not exceed 0.120 ppm ambient ozone for 1 hour, not to be exceeded more than once per calendar year on average over a 3-year period.104 The federal accedence level is ⱖ0.125 ppm averaged over 1 hour or ⱖ0.085 ppm averaged over 8 hours.104 During 1991 through 1993, ozone levels exceeded 0.085 ppm over 8 hours on 4 or more occasions in 394 counties and cities; an estimated 136 million persons (54.7% of the US population) resided in these areas.104

Curr Probl Pediatr Adolesc Health Care, January 2003

Studies have shown that exposure to ozone can produce cough, chest pain, upper respiratory tract irritation, and decreased lung function.105,106 A study from Los Angeles schools found that an increase of 20 ppb of O3 was associated with a 62.9% increase in absence rates for any illness and an 82.9% increase for respiratory illness. Neither NO2 nor particulate matter (PM10) levels were significantly related to absences.107 In a Canadian study, after controlling for sulfur dioxide, nitrogen dioxide, carbon monoxide, and other variables by multivariate analysis, high daily ozone concentrations the day prior to admission was positively associated with admissions for respiratory illness.108 A California study observed the lifetime effects of exposure to ambient ozone in college freshmen at Berkeley (nonasthmatics and nonsmokers) who were lifetime residents of San Francisco or Los Angeles, California. The authors found an association between ozone and decreasing pulmonary functions.109 Seasonal patterns of asthma deaths have been identified. One study observed that deaths in persons 5 to 35 years old peaked in June through August, which was consistent with an increase in the ozone levels.110 Evidence that changes in commuting behaviors can positively affect air quality and asthma exacerbations was noted in a 1996 study during the summer Olympic games in Atlanta, Georgia. The authors compared the 17 days of the Olympic games with a baseline period 4 weeks before and 4 weeks after the games and found that decreased traffic density was associated with a prolonged reduction in ozone pollution and significantly lower rates of childhood asthma events.111 Many communities monitor ozone levels. The US EPA has a color-coded air quality index of health categories and recommendations for protection. See Table 2 for the Air Quality Index that can be found at www.cleanairaction.org.112

Food Infectious The CDC estimates that there are 76 million cases of foodborne illness, “with 300,000 hospitalizations and 5000 deaths each year.”113 Estimated annual costs from medical expenses and productivity loss secondary to foodborne illness are between $5 and $23 billion per year.114 Microorganisms and their toxins, marine

11

TABLE 2. Air quality index

200 ppb

Code purple

150 ppb

Very unhealthy Code red

100 ppb

Unhealthy Code orange

50 ppb 0

Unhealthy for sensitive groups Code yellow Moderate Code green Good

Active children and adults and people with respiratory disease such as asthma should avoid all outdoor exertion; everyone else should limit outdoor exertion. Active children and adults and people with respiratory disease such as asthma should avoid prolonged outdoor exertion; everyone else should limit prolonged outdoor exertion. Active children and adults and people with respiratory disease such as asthma should should limit prolonged outdoor exertion. Unusually sensitive people should consider limiting prolonged outdoor exertion. No health effects are expected within this range.

Ozone is measured in parts per billion (ppb).

organisms and their toxins, fungi and their toxins, and chemical contaminants can cause illness, but the major sources of foodborne disease are fresh produce, meat, and poultry. Data from FoodNet USA, a community surveillance system for foodborne disease, found that bacterial causes account for most hospitalizations (60%) for foodborne illnesses, and 70% of deaths. The major causes in 1999 were Norwalk virus, 67%; Campylobacter, 14%; Salmonella, 10%; Clostridium perfringens, 2%; and Staphylococcus aureus, 1%. Prevention of bacterial foodborne illnesses is under the jurisdiction of the Food Safety and Inspection Service (FSIS). Established in 1981 by the US Department of Agriculture (USDA), it sets standards for the safety of meat, poultry, and eggs. The Food and Drug Administration (FDA) monitors other foods. The goal of the FSIS is to “reduce the risk of foodborne illness associated with the consumption of meat and poultry products.” Starting in 1998, the USDA started the Hazard Analysis and Critical Control Points (HACCP) system. The meat, poultry, seafood, and many juice production industries are now required to implement HACCP systems to prevent food safety hazards. The agency also inspects all meat and poultry sold in interstate and foreign commerce, including imported products. The FSIS can also test for the presence of pathogenic microorganisms and drug and chemical residues. Persons with questions about meat or poultry safety can access their site at www.fsis.usda.gov. Irradiation. Food irradiation is another preventive measure. It is a process by which food is exposed to ionizing radiation to prolong shelf life and reduce food losses, improve microbiologic safety, and/or reduce the use of chemical fumigants and additives. Use of ionizing radiation in food preservation was proposed

12

shortly after X-rays were discovered in 1895. It has been approved for use in selected foods in the United States since 1963. Four sources of radiation are authorized for food treatment: cobalt 60, cesium 137, machine-generated accelerated electrons, and machine-generated x-rays.115–117 In the United States, the most common source for food irradiation is cobalt 60, whose byproduct is the nonradioactive element nickel. Radiation kills primarily by fragmenting the DNA of the microbe. Thus, insects and parasite are most sensitive to destruction, and spores, prions, toxins, and viruses are most resistant. Spoilage bacteria (bacteria that alter the color, flavor, texture, or smell of food but do not cause human disease) are also sensitive. All foods are exposed to natural background radiation and are naturally radioactive. Irradiation of food does not increase its radioactivity because the process used for food is limited to sources producing energy too low to induce subatomic particles. Neither the food nor the packaging materials become radioactive.118 – 121 Irradiation of any food up to an overall average dose of 10 kGy presents no toxicologic hazards; hence, toxicologic testing of foods so treated is no longer required.122 However, like all forms of food processing, irradiation affects nutritional content. Vitamin loss is the largest nutritional concern and can be compounded by additional heat, such as cooking. Changes are similar to those from cooking, canning, pasteurizing, and other forms of heat processing.123 All irradiated foods sold in the United States must be clearly labeled with the international irradiation symbol, the Radura, and the words, “treated by irradiation, do not irradiate again” or “treated with radiation, do not irradiate again.”

Curr Probl Pediatr Adolesc Health Care, January 2003

Preventing foodborne disease requires efforts all along the chain, from farm, processing, and slaughter, to the consumer. Individuals can put prevention into the kitchen. Meats should be thoroughly cooked, at a core temperature of 165°, and until the juices run clear. Separate cutting utensils and boards should be used for meats and produce. Fruits and vegetables should be washed. Parents should avoid letting their children eat batters and dough that contain raw egg.

Noninfectious The AAP Green Book groups toxic chemicals in foods into 3 categories: (1) residues of pesticides deliberately applied to food crops or stored or processed foods; (2) colorings, flavorings, and other chemicals deliberately added to foods during processing; and (3) chemicals that inadvertently enter the food supply, such as aflatoxins, nitrites, polychlorinated biphenyls (PCBs), heavy metals including mercury, and pesticide residues such as dichlorodiphenyltrichloroethane (DDT).1 Mercury. Inorganic forms include elemental mercury (Hg0) and the salts (mercurous Hg1⫹ and mercuric Hg2⫹). The mercuric form can bind to carbon and form organomercury compounds including methyl, ethyl, and phenyl mercury, although phenyl mercury behaves like inorganic mercury because of its unstable carbon–mercury bond. Discarded or incinerated mercury thermometers are the largest source of mercury in the solid waste stream. One broken thermometer spills enough mercury to contaminate an entire lake. It then becomes available for methylation to methylmercury (MeHg) by microorganisms in the water. Diet is the major source of mercury exposure, primarily through the consumption of fish. Fish with higher mercury content tend to be carnivorous species such as pike in freshwater and shark, swordfish, tuna, and walleye in marine water. In general, freshwater fish have a higher mercury content. Much of what is known about the clinical effects of mercury poisoning was learned from poisonings that occurred in Japan and Iraq. In the 1950s, an epidemic of cerebral palsy occurred in children whose mothers had eaten contaminated fish. The source of contamination was mercury that had been discharged from a vinyl chloride factory into Minamata Bay.124 In the 1970s, an epidemic of psychomotor retardation, seizures, blindness, and deafness occurred in Iraqi children. The source of poisoning was grain that had been

Curr Probl Pediatr Adolesc Health Care, January 2003

treated with a MeHg-containing fungicide. The grain was used to make bread.125,126 Mercurous salts are also toxic. Calomel, a powder containing mercurous chloride (HgCl), was formerly used in teething powders.127 Ingestion led to acrodynia or “pink disease,” a hypersensitivity to the mercurous salts. Children had pain and swelling in the fingers and toes, a pink-colored rash, splenomegaly, lymphadenopathy, listlessness, irritability, failure to thrive, profuse perspiration, loss of teeth, and sometimes scarlet discoloration of the cheeks and the tip of the nose. It has also been reported in children after exposure to phenylmercury (used as a fungicidal diaper rinse) and to interior latex paint.95,128 The diagnosis of organic mercury poisoning is difficult. Since the half-life of mercury in blood is only 3 days, blood analysis is only useful for acute exposures. Urine measurements are similarly useless because organic mercury is excreted through the biliary system. Hair analysis can provide evidence of MeHg exposure. Supportive care is all that is available to patients with organic mercury poisoning. No specific treatment exists. Because central nervous system damage is permanent, prevention is key. The FDA advises young women, nursing mothers, pregnant women, and women of childbearing age who might be pregnant not to eat king mackerel, shark, swordfish, and tilefish because they contain high levels of MeHg. Small portions (12 ounces) per week of shellfish, canned fish, smaller ocean fish, or farm-raised fish are permitted. Women who eat fish caught by family and friends should check with their state or local health department for advice on the safety of fish from local waters. Specific advice and contact information for individual states is available through the website www.epa.gov/ ost/fish. The FDA regulation for mercury in fish is 1 ppm (1000 ppb). To further reduce potential exposure to mercury, the AAP recommends that health care providers and parents stop using mercury-containing devices.129 Manufacturers and retailers are following. Becton Dickinson & Co, the largest manufacturer of glass mercury thermometers, stopped making mercury thermometers in 2001. At the prompting of Health Care Without Harm, a nonprofit environmental protection advocacy group, many major retailers are removing mercury thermometers from their shelves. Local governments in several cities, including San Francisco,

13

TABLE 3.

Pesticides commonly found in the United States

Chemicals Organochlorines Organophosphates Carbamates Pyrethoids Herbicides Bi(Di)pyridyl Other

Examples

Toxic effects

DDT, lindane, dieldrin, chlordane Parathion, chlorpyrifos Malathion, aldicarb Cyfluthrin, permethrin, fenvalerate

Carcinogenic, endocrine disruptors, neurotoxic Neurotoxic, dermatotoxic Neurotoxic, dermatotoxic Endocrine disruptors, possibly immunotoxic and neurotoxic

Paraquat, diquat Atrazine, alachlor

Pulmonary fibrosis Carcinogenic

California; Ann Arbor, Michigan; and Duluth, Minnesota, have banned mercury-containing thermometers.130 Although injected rather than ingested, thimersol is an organic mercury compound that was used as a preservative in diphtheria, tetanus, pertussis, influenza, and hepatitis B vaccines. In July 1999, the AAP recommended the removal of thimersol from vaccines. By early 2001, all vaccines included in the recommended childhood immunization schedule that are routinely administered to children up to 6 years of age in the United States are available without thimersol. The Institute of Medicine’s Immunization Safety Committee states that current scientific evidence neither proves nor disproves a link between thimersol and neurodevelopmental disorders such as autism, attention deficit disorder, and speech delay in children.131 Nitrates and nitrites. Nitrate (NO3⫺) and nitrite (NO2⫺) are inorganic ions that are part of the nitrogen cycle. Microbes decompose organic nitrogen in soil and water to form ammonia, nitrate, and nitrite. Nitrates are not toxic but can be converted to toxic nitrites by intestinal microbes. The nitrite is reabsorbed into the blood, where it reacts with the ferrous (Fe2⫹) iron of deoxyhemoglobin, forming methemoglobin with iron in the ferric (Fe3⫹) state. Ferric iron cannot reversibly bind or transport oxygen. Hemoglobin protein may also be oxidized, causing denaturation and erythrocyte hemolysis and hemolytic anemia. Under usual circumstances, the liver metabolizes nitrates. Approximately 60% to 70% is excreted in the urine and 25% in the saliva. Physiologic methemoglobinemia levels average 1% to 2% of the total hemoglobin. Although food is rarely causes acute toxicity, food accounts for ⬎70% of nitrates in a typical diet. An additional 6% comes from meat and meat products in which sodium nitrite is used as a preservative and coloring agent. Most of the remaining portion is from contaminated water sources. (See section on Water.)

14

Infants younger than 4 months of age are at greatest risk for methemoglobinemia for several reasons. First, an infant’s higher gastric pH enhances the conversion of ingested nitrate to the more potent nitrite. Second, their NADH reductase system that reduces methemoglobin back to hemoglobin has only about 50% the activity of that present in an adult. Last, fetal hemoglobin is more readily oxidized to methemoglobin. Broccoli, cabbage, carrots, cauliflower, celery, and spinach are high in nitrites and should not be feed to children less than 3 months of age. In a study from Spain, 7 cases of methemoglobinemia were attributed to consumption of homemade mixed vegetables that included silver beets. The authors suggested that nitrituria in a cyanotic infant may suggest the diagnosis of methemoglobinemia.132 Nitrates are associated with diarrhea (of infectious origin or secondary to cow milk protein intolerance) and acidosis.133–136 (For diagnosis and treatment, see the section on Water.) There is no evidence that in breast-fed infants, methemoglobinemia develops from exposure to nitrates ingested by their mothers. Pesticides. Pesticides are substances that are used to prevent, destroy, or repel pests. They are also used as plant regulators or defoliants. They include fungicides, herbicides, insecticides, insect repellants, and rodenticides. Approximately 90% of American households use pesticides. The EPA estimates that each year domestic users in the United States spend $8.5 billion for 1.1 billion pounds of pesticide-active ingredients.137 The major classes of insecticides are organophosphates, carbamates, organochlorines, and pyrethrum and synthetic pyrethroids. Pesticides found in the United States are shown in Table 3. Because they persist in the environment and concentrate up the food chain, many organochlorine pesticides have been banned. The organophosphate and carbamate pesticides are biodegradable and do not accumulate or concentrate in the food chain, but they have a greater

Curr Probl Pediatr Adolesc Health Care, January 2003

potential for acute toxicity in humans. Chlorpyrifos is an organophosphate insecticide that is used to control cockroaches, fleas, and termites. Studies by the EPA have shown it to be present in air samples of 83% to 97% of homes in Jacksonville, Florida, and in 30% to 40% of homes in Massachusetts.138 Organophosphate and carbamate compounds account for most pesticide-related poisonings. They are readily absorbed by inhalation, ingestion, and skin absorption, and symptoms develop within hours. Both inactivate acetylcholinesterase (AchE), which leads to a rapid accumulation of acetylcholine. Neurochemical transmissions in the cholinergic system are overstimulated and then paralyzed. An appropriate mneumonic to remember symptoms is SLUG-A-BUG: S ⫽ Skeletal muscle weakness, L ⫽ lacrimation, U ⫽ Unconsciousness, G ⫽ GI cramping, anorexia, nausea, vomiting, and involuntary defecation, A ⫽ Aspiration pneumonia, B ⫽ Breathing difficulties (wheezing, and paralysis of respiratory muscles, U ⫽ Urination, G ⫽ Giddiness (psychosis and confusion). The symptoms depend on the route of exposure and the balance between muscarinic (organophosphate and carbamate) and nicotinic (organophosphate) receptors. The diagnosis of pesticide-related illness is suggested by history and physical examination and by including environmental causes in a differential diagnosis in a patient with the symptoms noted above. Additionally, the patient’s breath or clothing may have a petrochemical-like odor. Direct measurement of pesticide levels in blood and urine is usually only available from reference laboratories. Indirect measures such as acetylcholinesterase enzymes in red blood cells (true cholinesterase) and in plasma (pseudocholinesterase) are more readily available. General measures for the treatment of an acute ingestion include gastric lavage. A blood specimen for cholinesterase determination should be obtained. Physicians managing ingestions should contact a poison control center for guidelines regarding the antidotes, atropine and pralidoxime (2-PAM). After establishing an airway, intravenous atropine is administered and repeated at periodic intervals until signs of atropinization appear (eg, reversal of excessive salivation, bronchial secretions, and sweating). Atropinization is then maintained for the following 24 hours. However, atropine has no effect on the nicotinic or central nervous system manifestations. If a patient has muscle weakness, twitching, or respiratory depression, 2-PAM is needed. The dose is repeated at 10- to

Curr Probl Pediatr Adolesc Health Care, January 2003

12-hour intervals. Because 2-PAM reactivates enzyme activity, plasma cholinesterase levels can be monitored to determine its effect. If 2-PAM is not given within 24 to 48 hours, the AchE bond becomes irreversible, and recovery depends on “de novo” synthesis of AchE, which may take up to 3 months. Carbamate pesticides produce a shorter toxicity than organophosphates, so 2-PAM is rarely required. Protective clothing (including rubber gloves) should be worn when decontaminating patients exposed to organophosphate pesticides. Laundering may not be effective in removing the pesticide, so contaminated clothing may need to be burned. A rare organophosphate-induced distal neuropathy has been described with triorthocresyl phosphate (TOCP) and triorthotolyl phosphate (TOTP). One to 2 weeks after treatment of the acute toxicity, flaccidity or paralysis and paresthesias of the extremities occur that may persist for years. In 1959, several thousand people in Morocco were poisoned when jet fuel was mixed with olive oil and sold as cooking oil.139 Also, pesticides contain solvent carriers such as toluene and xylene. They are labeled as inert ingredients because they are not active as pesticides. However, they may be as toxic as the active ingredients. Pyrethrum is an insecticide extracted from chrysanthemum flowers. Naturally occurring pyrethrins and synthetic pyrethroids produce rapid paralysis of an insect’s nervous system. This property makes them effective “knock-down” agents against flying insects. They are often combined with a synergist, such as piperonyl butoxide or another insecticide, to increase efficacy. Because the liver rapidly metabolizes these compounds, toxicity is quite low after ingestion. Contact dermatitis is the most common hypersensitivity reaction and can occur after handling chrysanthemum flowers or exposure to synthetic pyrethroids. Descriptions range from local erythema resembling sunburn to a vesicular eruption similar to poison ivy and rarely, large bullae formation.140 Asthmatic-like reactions have also been reported. Synthetic pyrethroids are less likely to result in allergic reactions than preparations made from pyrethrum powder.141,142 One of the most common insect repellents is DEET (N, N-diethyl-meta-toluamide). It is useful for mosquitoes, mites, midges, biting flies, fleas, and ticks but has little effect on wasps, hornets, or bees. DEET functions by producing a vapor layer that is malodorous or distasteful to insects. A study of the relationship between DEET concentration and effectiveness

15

against mosquitoes showed that products with DEET concentrations of 50% were 95% effective for at least 4 hours and that higher concentrations provided little extra benefit.143 Therefore, products with concentration ⬎50% may not be needed for effective insect repellent. Adverse effects from the systemic absorption of DEET have been reported. In 1989, a report of seizure activity in 4 children and 1 adult attributed to DEET was published.144 For children, the AAP and the American Academy of Dermatology recommend products containing no more than 10% DEET. Because one of the primary routes of exposure to environmental risk for children is the diet, there are two federal statutes governing the use of pesticides in food: the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Under the FFDCA, maximum allowable residues, or tolerances, in food are established on a commodity-by-commodity basis by using a risk assessment framework. If there are multiple exposure pathways for a pesticide, exposure estimates need to be additive. Previously, if a specific pesticide was found in drinking water, in the home, or in food, each was allowed the full measure of allowable risk. Cumulative risk, exposure to pesticides with similar properties, is also aggregated under these laws. The laws also state that children’s safety should be assessed in terms of exposure and hazard of a pesticide. The EPA is required to put an additional 10-fold safety factor for protection of children unless there is evidence that it is safe. Also, the EPA classifies pesticides as “restricted” or “nonrestricted.” By law, restricted pesticides can be applied only by applicators that have passed a certification examination or by someone directly supervised by a certified applicator. New technologies that lead to less dependence on pesticides are being developed. Biopesticides result from the introduction of bacterial genetic material into plants. The result is an additional protein that adversely effects larvae development. One example is Bacillus thuringiensis (B.t.) insect-resistant cotton. A single gene from the bacterium B.t. is injected into cotton. The plant produces a protein that is toxic to the larvae. Another example is B.t. or transgenic corn. The altered corn plant reduces the need for multiple applications of pesticides. When insecticides or herbicides are used in row cropping, they need to be applied 4 or 5 times. With B.t. corn, only one application delivers the same effect. In the past, this method would have been called organic farming because of the reduced

16

use of chemicals. Now, organic farming specifically excludes genetically modified materials. Integrated pest management (IPM) is another new technology. It integrates both chemical and nonchemical methods to provide the least toxic alternative for pest control. Monitoring is used to determine if and when treatment is needed. Treatment may combine biological, cultural, educational, mechanical, and physical plans. Care givers can increase their awareness of pesticides and limit exposure by buying in-season produce to avoid exposure to imported and heavily sprayed items. For pesticides applied to the surface of foods, washing fruits and vegetables removes up to 60% of the pesticide residue. Peeling removes almost all the external residue but does not affect the internally absorbed portion. Proper labeling and storage of pesticides can reduce poisonings. Polychlorinated biphenyls. Polychlorinated biphenyls (PCBs) are a family of over 200 related synthetic 2-ringed organic oils with 1 to 10 substituted chlorine atoms. Because of their stability and low flammability, they have been used as insulating materials in electrical capacitors and transformers, hydraulic and lubricating fluids, plasticizers in waxes, ingredients in paper manufacturing, paints, adhesives, flame retardants, and for a variety of other industrial purposes. The diversity of their use, the large quantities used, and their stability has led to widespread occurrence of these compounds in soil and water. Both polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzodioxins (PCDDs or dioxins) are byproducts of PCBs and include some of the most toxic known synthetic chemicals. Because of their resistance to biodegradation, and the extreme toxicity of the byproducts, Congress banned their manufacture, sale, and distribution in 1977. Although PCBs are widespread in the aquatic environment, their low water solubility helps to prevent high concentrations in drinking water supplies. The principal source of human exposure is consumption of fish from contaminated waterways. Contamination occurs through a process known as bioaccumulation. The PCBs become increasingly concentrated as they move up the food chain from plankton to fish to humans. Once ingested, they are resistant to biological breakdown. Infants and children are more susceptible to the toxic effects of PCBs than adults. In utero, the PCBs readily cross the placenta, and after birth they are excreted Curr Probl Pediatr Adolesc Health Care, January 2003

into the breast milk. Nursing infants are at increased risk because human milk contains a steroid that inhibits PCB excretion. Studies on the neurodevelopmental effects of PCBs have shown that children whose mothers consumed an average of about two meals per month of lake trout or salmon from Lake Michigan prior to and during pregnancy had low birth weight, abnormal skin pigmentation, delayed developmental milestones, and lower than unexposed siblings.145,146 A study in Michigan found an adverse effect at age 4 years on the verbal and memory scale scores of the McCarthy Scales of Children’s Abilities.147 This effect appeared to be dose-dependent across a range of umbilical cord serum PCB levels. At age 11 years, the full-scale IQ was inversely associated with prenatal but not postnatal PCB exposure. One study even suggested that long-term exposure from fish consumption before pregnancy was more significant than consumption during pregnancy.148 PCBs have a very low potential for producing acute toxic effects. The only well-recognized postnatal effects are dermatologic and hepatic. Facial acneiform lesions develop weeks to months after exposure. Hyperpigmentation of the skin, conjunctivae, gingiva, and nails may also occur. Persons who have been chronically exposed to PCBs may have liver injury, which may present as weight loss, anorexia, nausea, vomiting, jaundice, and abdominal pain. Direct measurement of PCBs in the blood is not indicated unless the exposure has been massive. Diagnostic testing should be limited to liver function tests and a dermatologic examination, with skin biopsy of lesions. Because there is no specific treatment for PCB toxicity, education is the key to preventing the adverse effects of chemical exposure. States have local water advisories to alert anglers on particular waterways or fish. However, studies show that people who eat fish, including those who fish for food, were unaware of their states’ advisories or if they know, ignore them.149 –151 In 1998, the EPA and the ATSDR sent members of the medical community the brochure “Should I Eat the Fish I Catch? A Guide to Healthy Eating of the Fish you Catch.” It includes information on how to reduce health risk by selecting certain species or sizes of fish; trimming and cooking fish properly; and following fish consumption advisories. Health care providers can be alerted to their patients’ risk through both dietary and avocational histories. They can also advise parents to

Curr Probl Pediatr Adolesc Health Care, January 2003

limit their personal use of pesticides and to eat a varied diet. Currently, there is no legal maximum concentration for PCBs in drinking water. For food, the FDA mandates tolerances of 0.2 to 3.0 ppm PCBs for all foods, with a tolerance level in fish of 2 ppm.

Water Chlorination Byproducts Chlorination of water has been one of the 20th century’s greatest public health achievements. However, with cholera and typhoid diseases of the past, trihalomethanes (THMs) are of present concern. THMs include chloroform and other chlorinated compounds that are produced when chlorine reacts with natural organic contents (eg, humic and tannic acids). Studies have found an association between THMcontaining drinking water and increases in the rates of rectal and bladder cancer.152 The EPA decided that the cancer risk from chlorine byproducts is high enough that it reduced the maximum contaminant level to 0.1 mg/dL. Another disinfectant, chloramine (a chlorine and ammonia mixture) may decrease THM levels but has not been thoroughly investigated. However, the benefits of chlorinated drinking water in reducing waterborne diseases outweigh the small risks from traces of THMs.

Endocrine Disrupters Environmental endocrine disrupters include natural and synthetic compounds that can mimic hormones, disrupt hormones, or affect the endocrine system. Most disrupters are estrogenic. Examples of naturally occurring plant disrupters are the phytoestrogens coumesterol and genistein. Clover disease occurs in sheep that graze on red clover that contains coumesterol. Zerolanone is another disrupter that is a metabolite of the fungus Fusarium. Man-made compounds include DDT, PCBs, and nonylphenols. One form of dichlorodiphenyldichloroethane (DDE) is an antiandrogen. PCB’s are toxic to the developing thyroid and occupy a thyroid hormone receptor. Nonylphenols are compounds used in plastics that are hormonally active. (See Table 4.) The most commonly used weed killer (herbicide) used in the United States, atrazine, has been shown to disrupt the sexual development of frogs. Researchers found that concentrations 30 times lower than the

17

TABLE 4. Chemicals associated with reproductive and endocrine-disrupting events

Insecticides Carbaryl Chlordane Dicofol Dieldrin DDT/metabolites Endosulfan Heptachlor ␤-Hexachlorohexane ␥-Hexachlorohexane Methomyl Methoxychlor Mirex Oxychlordane Parathion Synthetic pyrethroids Toxaphene Transnonachlor

Industrial chemicals

Fungicides

Herbicides

Nematocides

Bisphenol A Benzo(a)pyrene Cadmium Dioxin (2,3,7,8-TCDD) Lead Mercury PBBs Pentachlorophenyl Penta-nonylphenols Phthalates Styrenes

Benomyl Hexachlorobenzene Mancozeb Metiram complex Tributyl tin Zineb Ziram

2,4-D 2,4,5-T Alachlor Amitrole Atrazine Metribuzin Nitrofen Trifluralin

Aldicarb Dibromo-chloropropane

www.atsdr.cdc.gov.

current allowable limit in drinking water produced male frogs with testosterone levels below those found in normal female frogs. Many had more than the normal number of sexual organs or had both male and female organs. The findings support the use of amphibians as environmental sentinels (http://www.scientificamerican.com/news/041602/1.html). In 1998, Congress implemented legislation requiring the EPA to screen and test chemicals in food and water for estrogenic and possibly other hormonal activity.

Nitrates Nitrates contaminate water supplies as the result of ground applications of fertilizers and seepage from septic tanks. Concentrations tend to be highest in rural, agricultural areas and may vary widely, based on seasons. The EPA has estimated that as many as 52% of community water wells and 57% of the domestic water wells in the United States are contaminated by nitrates (accessed at www.epa.gov/seahome/groundwater/src/overview.htm). Although water is a minor source of nitrate in an adult diet, it is the major source of exposure for formula-fed infants. Infants fed formula diluted with water from rural domestic wells are at greatest risk. The signs and symptoms of methemoglobinemia correlate with the percentage of total hemoglobin in the oxidized form. (See Table 5.) The diagnosis is suggested when a drop of blood placed on filter paper turns chocolate brown or slate gray. However, the most useful diagnostic test is a blood methemoglobin level. The percent oxygen saturation is a nonspecific finding, and measurement of

18

TABLE 5. Signs and symptoms of methemoglobinemia

Concentration 10%–20% 20%–45% 45%–55% ⬎70%

Clinical findings Central cyanosis, usually asymptomatic CNS depression (headache, dizziness, fatigue, lethargy, syncope) Coma, arrhythmias, shock, convulsions High risk of death

blood nitrate or nitrites in blood, urine, or saliva is not clinically useful. The denatured hemoglobin protein is seen in the peripheral blood smear as Heinz bodies. Patients with levels ⬍20% usually respond to eliminating the exposure. Patients with higher levels are treated with 100% oxygen and or a 1% intravenous solution of methylene blue. The methylene blue acts as a cofactor for NADPH-dependent methemoglobin reductase and results in the conversion of ferric iron in methemoglobin to ferrous iron with normalization of oxygen binding. After intravenous treatment with methylene blue, oral ascorbic acid or oral methylene blue should be given. Methylene blue should be avoided in patients with glucose-6-phosphate dehydrogenase deficiency asbecause it may result in hemolytic crisis. In cases of severe methemoglobinemia and/or contraindication to methylene blue, hyperbaric oxygen and exchange transfusion can be considered. Treatment must be accompanied by identification and elimination of the nitrate source. To prevent methemoglobinemia in infants, the “no observed adverse effect level” in drinking is 45 ppm (or mg/mL) for total nitrate or 10 ppm as nitrogen in nitrate.

Curr Probl Pediatr Adolesc Health Care, January 2003

Specific Contaminants and Diseases Lead Lead is a naturally occurring element. Children are exposed to lead from many sources (paint, vehicle exhaust, food (cans and ceramics), water, and ceramics) and through different pathways (air, food, water, dust and soil). In 1975, the EPA classified lead as a criteria pollutant, a designation reserved for pollutants whose public health impact is such that control is required by ambient standards rather than by specific emission controls. In 1976 and in 1984, the EPA ordered the reduction of almost all lead in gasoline. In 1990, amendments to the Clean Air Act completely prohibited the use of lead as a gasoline additive. The process was phased in between 1992 and 1995. However, since lead does not biodegrade or decay, exposure still occurs when children come in contact with contaminated soil. Normal mouthing behavior in children as well as pica (the repeated ingestion of nonfood substances) occurs with paint chips and dirt in children. Although manufacturers were required to remove lead from paint in 1977, it is still present in older

TABLE 6. The ABCs of lead poisoning (ATSDR)

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Anemia, abdominal pain Basophilic stippling Colic, constipation Dementia, developmental delay Encephalopathy Fatigue, fine motor coordination2, foot drop (wrist drop) Gingival pigmentation, gout, growth2 Headache, hearing2, hypertension Infertility, IQ2 Jittery Kills Low birth weight Miscarriages Nephropathy Oligospermatogenesis Prematurity Quantitative EEG changes Reading disability Seizures, stillbirths Tremor Uric acid1 Vitamin D2, vomiting Weight loss X-ray (lead lines or growth arrest lines in long bone films) Youth at risk aZarcon (Mexican folk remedy for colic), ZZP (zinc protoporphyrin—screening test before blood lead levels (BLL) directly measured)

TABLE 7. Class of child and recommended action according to blood lead measurement

Class

Blood lead levels (BLL) (␮g/dL)

I IIA

ⱕ10 10–14

IIB

15–19

III

20–44

IV

45–69

V

ⱖ70

Action No action required. Obtain a confirmatory venous BLL within 1 month; if still within this range, educate caregivers to decrease lead exposure. Repeat BLL in 3 months. If many children in the community have BLLs ⱖ10 ␮g/dL, community interventions (primary prevention activities) should be considered. Obtain a confirmatory venous BLL within 1 month; if still within this range, take a careful environmental history to assess possible high-dose sources of lead and educate care givers to decrease lead exposure and absorption. Repeat BLL test within 2 months. Obtain a confirmatory venous BLL within 1 week; if still within this range, conduct a complete medical history (including environmental evaluation and nutritional assessment and physical examination and educate care givers to decrease lead exposure and absorption. Either refer the patient to a local health department or provide case management that should include a detailed environmental investigation with lead hazard reduction and appropriate referrals for support services. If BLL ⬎25 ␮g/dL, consider chelation (not currently recommended for BLLs ⬍45 ␮g/dL) after consultation with clinicians experienced in lead toxicity treatment. Obtain confirmatory venous BLL within 2 days; if still within this range, conduct a complete medical history (including environmental evaluation and nutritional assessment and physical examination), educate care givers to decrease lead exposure and absorption. Either refer the patient to the local health department or provide case management that should include a detailed environmental investigation with lead hazard reduction and appropriate referrals for support services. Begin chelation therapy in consultation with physicians experienced in lead toxicity therapy. Hospitalize the patient and begin medical treatment immediately in consultation with physicians experienced in lead toxicity therapy. Obtain a confirmatory BLL immediately. The rest of treatment should be as noted for treatment of children with BLL between 45 and 69 ␮g/dL.

Curr Probl Pediatr Adolesc Health Care, January 2003

19

TABLE 8. Pediatric environmental health specialty units

Location

States and territories covered

Boston

CT, MA, ME, NH, RI, VT

New York City

NJ, NY, Puerto Rico, Virgin Islands

Washington DC

DC, DE, MD, PA, VA, WV

Atlanta

AL, FL, GA, KY, NC, MS, SC, TN

Chicago

IL, IN, MI, MN, OH, WI

Tyler

AR, LA, NM, OK, TX

Iowa City

IA, KS, MO, NE

Denver Irvine and San Francisco

CO, MT, ND, SD, UT, WY AZ, CA, HI, NV, American Samoa, Guam, Trust Territory of the Pacific Islands AK, ID, OR, WA

Seattle

Edmonton, Alberta, Canada

Canadian provinces

homes. Children can be exposed when the paint chips or peels or when the home is renovated. Inadvertent ingestion also occurs through the consumption of foods in lead-soldered cans. In 1980, almost 50% of domestically produced food and soft drink cans were lead-soldered. By 1989, the use of lead-soldered cans declined to 1.4% of domestically produced cans. However, imported foods may still be in lead-soldered cans. Exposure to contaminated water occurs when lead is leached from leaded pipes. Lead pipes are found in residences built before the 1920s, and copper pipes soldered with lead came into general use in the 1950s. Absorption varies by the route of exposure; when inhaled, there is almost complete absorption; when ingested, almost 50% is absorbed. Once in the blood, lead is distributed to soft tissues (kidney, bone marrow, liver, and brain) and mineralizing tissues (bones and teeth). Lead poisoning is silent. Most children have no symptoms, but almost every system in the body is affected. (See Table 6.) The most sensitive target is the nervous system. Small effects in many children may have a greater cumulative impact than large effects in small number of children. For instance, a 4- to 6-point median change in a population with a median IQ approximately 100 can result in a 4-fold increase in the

20

Telephone number (888) (888) (866) (212) (866) (202) (877) (877) (404) (800) (312) (888) (903) (866) (866) (319) (877) (866) (866) (877) (877) (206) (780)

CHILD-14 244-5314 265-6201 241-6173 622-4231 994-1166 33 PEHSU 337-3478 727-9483 672-3113 633-5310 901-5665 531-0830 MWR-PEHC 697-7342 384-8311 800-5554 UC-PEHSU 827-3478 KID-CHEM 543-2436 526-2121 930-5731

number of developmentally delayed persons in that population.153 As studies continue to document the deleterious effects of lead at lower and lower levels, the level of concern has steadily been lowered from ⬎60 ␮g/dL of blood in 1971 to 25 ␮g/dL in 1985 to 10 ␮g/dL in 1991.154 For testing, venipuncture is the preferred method. However, one study demonstrated that capillary sampling might be as accurate.155 Screening recommendations vary. The CDC recommends universal screening for communities with 27% or more of the housing built before 1950 and in populations in which the percentage of 1- and 2-yearolds with elevated blood lead levels (BLL) is 12% or more.156,157 In areas that have newer homes or fewer children with elevated BLLs, selective screening is sufficient. Although there is no safe BLL, the CDC has divided BLLs into 5 categories with corresponding recommendations for treatment. (See Table 7.) Several drugs have been used in the treatment of lead poisoning. They work by binding or chelating lead. Prior to 1991, all agents were administered intramuscularly or intravenously. In January 1991, the FDA approved succimer, an oral chelating agent, for the treatment of children with BLLs ⬎45 ␮g/dL. As with previous chelating agents, succimer should only be

Curr Probl Pediatr Adolesc Health Care, January 2003

TABLE 9. Home inventory questionnaire

Where does the child live or spend time? What is the age and condition of the home? Are the windowsills peeling? Are you renovating a room or planning to? Do you have a basement? Are there sleeping or playing areas in the basement? Do you have water damage or visible mold in any part of your home? Do you live in a mobile home? Do you have a woodstove or fireplace? Does smoke enter the room when you use it? Do you have a gas stove? Does it have a pilot light? Do you use the stove for additional heat? Do you use pesticides on your lawn or use a proprietary lawn service? Do you use pesticides in your home? Is your home located near a polluted lake or stream, industrial area, highway, dump site, farm, etc.? Smoking Does anyone in the home smoke? How many people? Is smoking allowed by visitors to your home, or in the car? Diet: water and food Is your baby breast-feeding? Do you use well water? Do you use tap water? Do you wash fresh fruits and vegetables? Do you use dietary supplements or ethnic remedies? Job-related hazards What do you and your spouse do for a living? Does your job or your spouse’s job involve contact with metals, dust, chemicals or fibers? Do teenagers in the home work? Hobbies Are you or your child involved in a hobby at home? Data from Etzel RA, Balk SJ, eds. American Academy of Pediatrics Handbook of Environmental Health. Elk Grove Village, IL: American Academy of Pediatrics; 1999. p. 22–23.

given to children who reside in lead-free environments during and after treatment. Progress has been made in reducing environmental sources of lead. The gradual elimination of lead from gasoline between 1970 and 1995 has correlated with declines in BLLs of children and adults.158

Resources Pediatric Environmental Health Specialty Units There are 10 pediatric environmental health specialty units throughout the United States. They are government-funded centers that specialize in pediatric environmental health and are staffed by professionals in pediatrics, toxicology, and occupational-environmental medicine. Specialists provide telephone consultations, receive clinical referrals, and conduct training in the diagnosis and treatment of illnesses that are or may be associated with exposure to toxic substances and other environmental risks. They can also provide guidance in the event of chemical spills, environmental emergencies, or other uncontrolled releases, such as from waste sites or terrorist attacks. (See Table 8.)

Curr Probl Pediatr Adolesc Health Care, January 2003

Conclusion The protection of children from environmental threats requires a broad-based approach. First, we must develop a better understanding of how children’s exposure and susceptibility changes over time. Second, we must take into account cumulative and aggregate exposures. Last, we must develop an epidemiologic approach. We need to study cause-and-effect relations between exposure and disease to justify the development of policies that prevent disease. Health care providers can start with inquiries into a child’s environment through the home inventory. (See Table 9.)

References 1. Committee on Environmental Health, American Academy of Pediatrics. Handbook of pediatric environmental health. Elk Grove, IL: American Academy of Pediatrics; 1999. 2. National Academy of Sciences. Pesticides in the diets of infants and children. Washington, DC: National Academy Press; 1993. 3. Till C, Westall CA, Rovet JF, Koren G, et al. Effects of maternal occupational exposure to organic solvents on offspring visual functioning: a prospective controlled study. Teratology 2001;64:134-41. 4. Clemens PC, Neumann RS. The Wolff-Chaikoff effect:

21

5.

6.

7.

8.

9. 10.

11.

12.

13.

14.

15. 16.

17. 18.

19. 20.

21.

22.

23.

22

hypothyroidism due to iodine application. Arch Dermatol 1989;125:705. Shuman RM, Leech RW, Alvord EC. Neurotoxicity of hexachlorophene in the human: , I. A: a clinicopathologic study of 248 children. Pediatrics 1974;54:689-95. Wysowski DK, Flynt JW Jr, Goldfield M, Altman R, Davis A, et al. Epidemic neonatal hyperbilirubinemia and use of a phenolic disinfectant detergent. Pediatrics 1978;61:165-70. Martin-Bouyer G, Lebreton R, Toga M, Stolley PD, Lockhart J, et al. Outbreak of accidental hexachlorophene poisoning in France. Lancet 1982;1:91-5. Plunkett LM, Turnbull D, Rodricks JV. Differences between adults and children affecting exposure assessment. In: Buzelian PS, Henry CJ, Olin SS, editors. Similarities and differences between children and adults: implications for risk assessment. Washington, DC: ILSI Press; 1992. p. 79-94. Solomon LM, Fahrner L, West DP. Gamma benzene hexachloride toxicity. Arch Dermatol 1977;113:353-7. Lipscomb JW, Kramer JE, Leikin JB. Seizure following brief exposure to the insect repellent N,N-diethyl-m-toluamide. Ann Emerg Med 1992;21:315-7. Martinez F, Morgan W, Wright AL, et al. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med 1988;319:1112-7. Cunningham J, Duckery D, Speizer FE. Maternal smoking during pregnancy as a predictor of lung function in children. Am J Epidemiol 1994;139:1139-52. Hanrahan J, Tager IB, Segal MR, et al. Effect of maternal smoking during pregnancy on early infant lung function. Am Rev Respir Dis 1992;145:1129-35. Farrow JR, Davis GJ, Roy TM, et al. Fetal death due to nonlethal maternal carbon monoxide poisoning. J Forens Sci 1990;35:1448-52. Luyens JN. The legacy of well-water methemoglobinemia. JAMA 1987;257:2793-5. US Environmental Protection Agency. Review of the National Ambient Air Quality Standards for Lead: Exposure Analysis Methodology and Validation. US EPA: Air Quality Management Division, Office of Air Quality Planning and Standards; 1989. Bakir F, Damluji SF, Amin Zaki L, et al. Methylmercury poisoning in Iraq. Science 1973;181:230-41. Marsh DO, Myers GJ, Clarkson TW, et al. Fetal methylmercury poisoning: clinical and toxicological data on 29 cases. Ann Neurol 1980;7:348-53. Byer A, Traylor TR, Semmer JR. Acetaminophen overdose in the third trimester of pregnancy: JAMA 1982;247:3114-5. Nicholson WJ, Perkel G, Selikoff IJ. Occupational exposure to asbestos: population at risk and projected mortality: 1980 –2030. Am J Ind Med 1982;3:259-311. Agency for Toxic Substances and Disease Registry. Toxological profile for asbestos. Atlanta: US Department of Health and Human Services, Public Health Service; 1995. American Academy of Pediatrics Committee on Environmental Hazards. Asbestos exposure in schools. Pediatrics 1987;79:301-5. Dekker H. Asthma und Milben, Munch Med Wochenschr 1928;75:515 (Translated in J Allergy Clin Immunol 1971; 48:25-4).

24. Kang B, Vellody D, Homburger H, et al. Cockroach: cause of allergic asthma: its specificity and immunologic profile. J Allergy Clin Immunol 1979;63:80-6. 25. Gelber LE, Seltzer LH, Bouzoukis JK, et al. Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital. Am Rev Respir Dis 1993;147:573-8. 26. Lehrer SB, Aukrust L, Salvaggio JE. Respiratory allergy induced by fungi. Clin Chest Med 1983;4:23-41. 27. Platts MT, Tovey ER, Mitchell EB, et al. Long-term effects of living in a dust-free room on patients with allergic asthma: reversal of bronchial hyperreactivity. Monogr Allergy 1983; 18:153-5. 28. Murray AB, Ferguson AC. Dust-free bedrooms in the treatment of asthmatic children with house dust or house dust mite allergy: a controlled trial. Pediatrics 1983;71:418-22. 29. Lintner TJ, Brame KA. The effects of season, climate, and air-conditioning on the prevalence of Dermatophagoides mite allergens in house dust. J Allergy Clin Immunol 1993;91:862-7. 30. Wood RA, Chapman MD, Adkinson NF Jr, et al. The effect of cat removal on allergen content in household dust samples. J Allergy Clin Immunol 1989;83:730-4. 31. DeBlay F, Chapman MD, Platts-Mills TAE. Airborne cat allergen (Fel d I): environmental control with the cat in situ. Am Rev Respir Dis 1991;143:1334-9. 32. Strachan DP, Flannigan B, McCabe EM, et al. Quantification of airborne moulds in the homes of children with and without wheeze. Thorax 1990;45:382-7. 33. Maier WC, Arrighi HM, Morray B, et al. Indoor risk factors for asthma and wheezing among Seattle school children. Environ Health Perspect 1997;105:208-14. 34. O’Hollaren MT, Yunginger JW, Offord KP, et al. Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma. N Eng J Med 1991;324:359-63. 35. Dearborn DG, Yike I, Sorenson WG, et al. Overview of investigations into pulmonary hemorrhage among infants in Cleveland, Ohio. Environ Health Perspect 1999;107(Suppl 3):495-9. 36. Flappan SM, Portnoy J, Jones P, et al. Infant pulmonary hemorrhage in a suburban home with water damage and mold (Stachybotrys atra). Environ Health Perspect 1999;107: 927-30. 37. Elidemir O, Colasurdo GN, Rossman SN, et al. Isolation of Stachybotrys from the lung of a child with pulmonary hemosiderosis. Pediatrics 1999;104:964-6. 38. Samet JM, Marbury MC, Spegler JD. Health effects and sources on indoor air pollution, Part I. Am Rev Resp Dis 1988;137:221-41. 39. Cobb N, Etzel R. Unintentional carbon monoxide-related deaths in the United States, 1979 through 1988. JAMA 1991; 266:658 – 63. 40. Seger D, Welch L. Carbon monoxide controversies: neuropsychologic testing, mechanism of toxicity, and hyperbaric oxygen. Ann Emerg Med 1994;97:165-9. 41. Wright AL, Holberg C, Martinez FD, et al, Group Health Medical Associates. Relationship of parental smoking to

Curr Probl Pediatr Adolesc Health Care, January 2003

42.

43.

44.

45.

46.

47. 48.

49.

50.

51.

52.

53.

54.

55. 56.

57. 58.

59.

60.

wheezing and nonwheezing lower respiratory tract infections illness in infancy. J Pediatr 1991;118:207-14. Chilmonczyk BA, Salmun LM, Megathlin KN, et al. Association between exposure to environmental smoke and exacerbations of asthma in children. N Engl J Med 1993;328: 1665-9. Martinez FD, Cline M, Burrows B. Increased incidence of asthma in children of smoking mothers. Pediatrics 1992;89: 21-6. Morgan W, Martinez F. Risk factors for developing wheezing and asthma in childhood. Pediatr Clin North Am 1992; 39:1185-203. Young S, LeSouef P, Geelhoed G, et al. The influence of a family history of asthma and parental smoking on airway responsiveness in early infancy. N Engl J Med 1991;324: 1168-73. Milberger S, Biederman J, Faraone SV, et al. Is maternal smoking during pregnancy a risk factor for attention deficit disorder in children? Am J Psychiatry 1996;153:1138-42. Hopper JL, Seeman E. The bone density of female twins discordant for tobacco use. N Engl J Med 1994;330:387-92. Ballard JE, Koepsell TD, Rivara F. Association of smoking and alcohol drinking with residential fire injuries. Am J Epidemiol 1992;135:26-34. Sandler DP, Everson RB, Wilcox AJ, et al. Cancer risk in adulthood from early life exposure to parents’ smoking. Am J Pub Health 1985;75:487-92. Christen WG, Glynn RJ, Ajani UA, et al. Smoking cessation and risk of age-related cataracts in men. JAMA 2000;284: 713-6. Sinha AK, Misra GC, Patel DK. Effect of cigarette smoking on lipid profile in the young. J Assoc Physicians India 1995;43:185-8. Khoury MJ, Gomez-Farias M, Mulinare J. Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring? AJDC 1989;143:333-7. Parks ET, Nicholson T. The effects of smokeless tobacco use on the prevalence of dental caries. Health Values 1990;14: 37-40. Frerichs RR, Aneshensel CS, Clark VA, et al. Smoking and depression: a community study. Am J Public Health 1981; 71:637-40. Anda RF, Williamson DF, Escobedo LG, et al. Depression and the dynamics of smoking. JAMA 1990;264:1541-5. Coste J, Job-Spira N, Fernandez H. Increased risk of ectopic pregnancy with maternal cigarette smoking. Am J Pub Health 1991;81:199-201. Andres RL, Day MC. Perinatal complications associated with maternal tobacco use. Semin Neonatol 2000;5:231-41. Alaswad B, Toubas PL, Grunow JE. Environmental tobacco exposure and gastroesophageal reflux l: reflux in infants with life-threatening events. J Okla State Med Assoc 1996;89:2337. Ballard T. Green tobacco sickness: occupational nicotine poisoning in tobacco workers. Arch Environ Health 1995; 50:384-89. Bastiaan RJ, Reade PC. The effects of tobacco smoking on oral and dental tissues. Aust Dent J 1976;21:308-15.

Curr Probl Pediatr Adolesc Health Care, January 2003

61. Ahmad N. Maternal-fetal transmission of human immunodeficiency virus. J Biomed Sci 1996;4:238-50. 62. Moskowitz WB, Mosteller M, Schieken RM, et al. Lipoprotein and oxygen transport alterations in passive smoking preadolescent children: the MCV twin study, Circulation 1990;81:586-92. 63. Lashner BA, Shaheen NJ, Hanauer SB, et al. Passive smoking is associated with an increased risk of developing inflammatory bowel disease in children. Am J Gastroenterol 1993;88:356-9. 64. Olds DL, Henderson CR, Tatelbaum R. Intellectual impairment in children of women who smoke cigarettes during pregnancy. Pediatrics 1994;93:221-7. 65. Smolinske SC, Spoerke DG, Spiller SK, et al. Cigarette and nicotine chewing gum toxicity in children. Hum Toxicol 1998;7:27-31. 66. World Health Organization. The world health report 1999: combating the tobacco epidemic. Geneva: WHO; 1999. 67. Mills PK, Newell GR, Beeson WL, et al. History of cigarette smoking and risk of leukemia and myeloma: results from the Adventist health study. J Natl Cancer Inst 1990;82:1832-6. 68. Gallego H, Crutchfield CE, Lewis EJ, et al. Report of an association between discoid lupus erythematosus and smoking. Cutis 1999;63:231-4. 69. Seddon JM, Willett WC, Speizer FE, et al. A prospective study of cigarette smoking and age-related macular degeneration in women. JAMA 1996;276:1141-51. 70. Fischer M, Hedberg K, Cardosi P, et al. Tobacco smoke as a risk factor for meningococcal disease. Pediatr Infect Dis J 1997;16:979-83. 71. Hopkinson JM, Schanler RJ, Fraley K, et al. Milk production by mothers of premature infants: incidence of cigarette smoking. Pediatrics 1992;90:934-8. 72. Centers for Disease Control. MMWR: Ingestion of cigarettes and cigarette butt by children: Rhode Island, January 1994July 1996. Morb Mortal Wkly Rep 1997;46:125-8. 73. Kahn A, Groswasser J, Sottiaux M, et al. Prenatal exposure to cigarettes in infants with obstructive sleep apneas. Pediatrics 1994;93:778-83. 74. Kitchens GO. Relationships of environmental tobacco smoke to otitis media in young children. Laryngoscope 1995;105: 1-13. 75. Ey JL, Holberg CJ, Aldous MB, et al. Passive smoke exposure and otitis media in the first year of life. Pediatrics 1995;95:670-7. 76. Naeye RL. Abruptio placentae and placenta previa: frequency, perinatal mortality, and cigarette smoking. Obstet Gynecol 1980;55:701-4. 77. Asmussen I. Ultrastructure of the villi and fetal capillaries in placentas from smoking and nonsmoking mothers. Br J Obstet Gynaecol 1980;87:239-45. 78. Colley JR, Holland WW, Corkhill RT. Influence of passive smoking and parental phlegm on pneumonia and bronchitis in early childhood. Lancet 1974;2:1031-4. 79. Ohmi H, Hirooka K, Mochizuki Y. Fetal growth and the timing of exposure to maternal smoking. Pediatr Int 2002;44:55-9. 80. Frankowski BL, Weaver SO, Secker-Walker RH. Advising parents to stop smoking: pediatricians’ and parents’ attitudes. Pediatrics 1993;91:296-300.

23

81. Mussalo-Rauhamaa H, Jaakola T. Plutonium-239, 240Pu and 210 Po contents of tobacco and cigarette smoke. Health Phys 1985;49:296-301. 82. Kakish KS, Mahafza T, Batieha A, et al. Clinical sinusitis in children attending primary care centers. Pediatr Infect Dis J 2000;19:1071-4. 83. Hakim RB, Tielsch JM. Maternal cigarette smoking during pregnancy: a risk factor for childhood strabismus. Arch Ophthalmol 1992;110:1459-62. 84. Haglund B, Cnattingius S. Cigarette smoke as a risk factor for sudden infant death syndrome: a population-based study. Am J Public Health 1990;89:29-32. 85. Klonoff-Cohen HS, Edelstein SL, Lefkowitz ES, et al. The effect of passive smoking and tobacco exposure through breast milk on sudden infant death syndrome. JAMA 1995; 273:795-8. 86. Said G, Zalokar J, Lellouch J, et al. Parental smoking related to adenoidectomy and tonsillectomy in children. J Epidemiol Community Health 1978;32:97-101. 87. Cameron P, Kostin JS, Zaks JM, et al. The health of smokers’ and nonsmokers’ children. J Allergy 1969;43:336-41. 88. Moskowitz WB, Mosteller M, Schieken RM, et al. Lipoprotein and oxygen transport alterations in passive smoking preadolescent children: the MCV twin study. Circulation 1990;81:586-92. 89. Schilling RSF, Letai AD, Hui SL, et al. Lung function, respiratory disease, and smoking families. Am J Epidemiol 1977;106:274-83. 90. Frischer T, Kuehr J, Meinert R, et al. Maternal smoking in early childhood: a risk factor for bronchial responsiveness to exercise in primary-school children. J Pediatr 1992;121:17-22. 91. Robertson PB, Walsh M, Greene J, et al. Periodontal effects associated with the use of smokeless tobacco. J Periodontol 1990;61:438-43. 92. Soldatos CT, Kales JD, Scharf MB, et al. Cigarette smoking associated with sleep difficulties. Science 1980;207:551-3. 93. Hudson PJ, Vogt RL, Brodnum J, et al. Elemental mercury exposure among children of thermometer plant workers. Pediatrics 1987;79:935-8. 94. Hirschmann SZ, Feingold M, Boylen G. Mercury in house paint as a cause of acrodynia: effect of therapy with N-acetylD,L-penicillamine. N Engl J Med 1963;269:889-93. 95. Agocs MM, Etzel RA, Parrish RG, et al. Mercury exposure from interior latex paint. N Engl J Med 1990;323:1096-101. 96. Vimy MJ, Lorscheider FL. Intra-oral mercury released from dental amalgam. J Dent Res 1985;64:1069-71. 97. Svare CW, Peterson LC, Reinhardt JW, et al. The effect of dental amalgams on mercury levels in expired air. J Dent Res 1981;60:1668-71. 98. Agency for Toxic Substances and Disease Registry. Toxicological profile for mercury. Atlanta: US Department of Health and Human Services, Public Health Service; 1989. 99. Harley N, Samet JM, Cross FT, et al. Contribution of radon and radon daughters to respiratory cancer. Environ Health Perspect 1986;70:17-22. 100. American Academy of Pediatrics Committee on Environmental Hazards: Radon exposure: a hazard to children. Pediatrics 1989;83:799-802. 101. Ritchie IM, Lehnen RG. Formaldehyde-related health com-

24

102.

103.

104. 105. 106.

107.

108.

109.

110. 111.

112. 113. 114. 115. 116.

117.

118. 119.

120.

121. 122.

plaints in residents living in mobile and conventional homes. Am J Public Health 1987;77:323-8. Committee on the Possible Effects of Electromagnetic Fields on Biological Systems, Board on Radiation Effects Research, National Research Council. Possible Health Effects of Exposure to Residential Electric and Magnetic Fields. Washington, DC: National Academy Press; 1997. Linet MS, Hatch EE, Kleinerman RA, et al. Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med 1997;337:1-7. CDC. Children at risk from ozone air pollution—United States, 1991–1993. MMWR 1995;44:309-12. Koren HS, Bronberg PA. Respiratory responses of asthmatics to ozone. Int Arch Allergy Immunol 1995;107:236-8. Ostro BD. Examining the acute health outcomes due to ozone exposure and their subsequent relationship to chronic disease outcomes. Environ Health Perspec Suppl 1993;101:213-6. Burnett RT, Brook JR, Yung WT, et al. Association between ozone and hospitalization for respiratory diseases in 16 Canadian cities. Environ Res 1997;72:24-31. Gilliland FD, Berhane K, Rappaport EB, et al. The effects of ambient air pollution on school absenteeism due to respiratory illness. Epidemiology 2001;12:43-54. Kunzli N, Lurmann F, Segal M, et al. Association between lifetime ambient ozone exposure and pulmonary function in college freshman: results of a pilot study. Environ Res 1997;72:8-23. Balmes JR. The role of ozone in the epidemiology of asthma. Environ Health Perspect Suppl 1993;101:219-24. Friedman MS, Powell KE, Hutwanger L, et al. Impact of changes in transportation and commuting behaviors during the 1996 summer Olympic games in Atlanta on air quality and childhood asthma. JAMA 2001;285:897-905. http://www.cleanairaction.org. Accessed April 22, 2002. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report March 17, 2000. Kaferstein FK, Moy GG. Public health aspects of food irradiation. J Public Health Policy 1993;14:133-6. Council for Agricultural Science, and Technology. Radiation pasteurization of food. April 1996. Issue Paper No. 7. American Academy of Pediatrics Committee on Environmental Health: Technical Report: Irradiation of Food. Pediatrics 2000;106:1505-10. Sun M. Renewed interest in food irradiation: FDA ponders approval as proponents push it as an alternative to pesticides. Science 1984;223:667-8. AAP Committee on Environmental. Irradiation of food. Pediatrics 2000;106:1505-10. From the International Atomic Energy Agency. Facts about food irradiation.Available at:http://www.iaea.org/worldatom/inforesource/other/food/q&a.html. Accessed November 19, 2002. World Health Organization. Safety and nutritional adequacy of irradiated food. Geneva, Switzerland: World Health Organization; 1994. Urbain WM. Food irradiation. Adv Food Res 1978;24:155-227. World Health Organization. Food irradiation: a technique for preserving and improving the safety of food. Geneva, Switzerland: World Health Organization; 1988.

Curr Probl Pediatr Adolesc Health Care, January 2003

123. Diehl J. Safety of irradiated food. 2nd ed. New York, NY: Marcel Dekker; 1995. 124. Powell PP. Minimata disease: a story of mercury’s malevolence. South Med J 1991;84:1352-8. 125. Bakir F, Damluji SF, Amin-Zaki L, et al. Methylmercury poisoning in Iraq. Science 1973;181:230-41. 126. Amin-Zaki L, Elhassani S, Majeed MA, et al. Perinatal methylmercury poisoning in Iraq. Am J Dis Child 1976;130: 1070-6. 127. Cheek DB. Acrodynia. In: Kelly V, editor. Brenneman’s practice of pediatrics. Vol I. New York, NY: Harper and Row Publishers; 1977. p. 1-14. 128. Gotelli CA, Astolfi E, Cox C, et al. Early biochemical effects of an organic mercury fungicide on infants: “dose makes the poison.” Science 1985;227:638-40. 129. AAP Committee on Environmental Health. Mercury in the environment: implications for pediatricians. Pediatrics 2001; 107:197-205. 130. Maudlin RK. Sale of mercury thermometers banned. BioMedicine 2001;4:86-7. 131. Institute of Medicine’s Immunization Safety Committee. http://www.nap.edu. Accessed November 19, 2002. 132. Sanchez-Echaniz J, Benito-Fernandez J, Mintegui-Raso S. Methemoglobinemia and consumption of vegetables. Pediatrics 2001;1024 – 8. 133. Hanukoglu A, Danon PN. Endogenous methemoglobinemia associated with diarrheal disease in infancy. J Pediatr Gastroenterol Nutr 1996;23:1-7. 134. Pollack ES, Pollack CV Jr. Incidence of subclinical methemoglobinemia in infants with diarrhea. Ann Emerg Med 1994;24:652-6. 135. Lebby T, Rocco JJ, Arcinue EL. Infantile methemoglobinemia associated with acute diarrheal illness. Am J Emerg Med 1993;11:471-2. 136. Murray KF, Christie DL. Dietary protein intolerance on infants with transient methemoglobinemia and diarrhea. J Pediatr 1993;122:90-2. 137. Schlerow LJ. Pesticide policy issues. Washington, DC: The Library of Congress; 1996. 138. Whitmore RW, Immerman FW, Camann DE, et al. Nonoccupational exposures to pesticides for residents of two US cities. Arch Environ Contam Toxicol 1994;26:47-59. 139. Abou-Donia MB, Lapadula DM. Mechanisms of organophosphorus ester-induced delayed neurotoxicity: type I and type II. Ann Rev Pharmacol Toxicol 1990;30:405-40. 140. McCord CP, Kilker CH, Minster DK. Pyrethrum dermatitis: a record of occurrence of occupational dermatosis among workers in the pyrethrum industry. JAMA 1921;77:448-9. 141. Garey J, Wolff MS. Estrogenic and anti-progestagenic activities of pyrethroid insecticides. Biochem Biophys Res Commun 1998;251:855-9. 142. Blondell J. Epidemiology of pesticide poisonings in the

Curr Probl Pediatr Adolesc Health Care, January 2003

143. 144.

145.

146.

147.

148.

149.

150.

151. 152.

153.

154.

155.

156.

157.

158.

United States, with special reference to occupational cases. Occup Med—State of the Art Rev 1997;12:209-20. Buescher MD. The dose-persistence relationship of DEET against Aedes aegypti. Mosquito News 1983;43:364-6. Oransky S. Seizures temporally related associated with use of DEET insect repellent: New York and Connecticut. MMWR 1989;38:678-80. Jacobsen JL, Jacobson SW. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. New Engl J Med 1996;335:783-9. Longnecker MP, Rogan WJ, Lucier G. The human effects of DDT (dichlorodiphenyltrichloroethane) and PCBs (polychlorinated biphenyls) and an overview of organochlorines in public health. Ann Rev Public Health 1997;18:211-44. Gladen BC, Ragan NB, Rogan WJ. Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodephenyl dicloroethene. J Pediatr 2000:136:490-6. Fein GG, Jacobson SW, Schwartz PM, et al. Prenatal exposure to polychlorinated biphenyls: effects on birth size and gestational age. J Pediatr 1984;105:315-20. Tilden J, Hanrahan L, Anderson H, et al. Health advisories for consumers of Great Lakes sport fish: is the message being received? Environ Health Perspect 1997;105:1360-5. May H, Burger J. Fishing in a polluted estuary: fishing behavior, fish consumption, and potential risk. Risk Anal 1996;16:459-71. Ramos A, Crain E. Potential health risk of recreational fishing in New York City. Amb Pediatr 2001;1:252-5. Morris RD, Audet Am, Angelillo IF, et al. Chlorination, chlorination by-products, and cancer: a meta-analysis. Am J Public Health 1992;82:955-63. Needleman HL, Gastonis CA. Low-level lead exposure and the IQ of children: a meta-nalysis of modern studies. JAMA 1990;263:673-8. Centers for Disease Control and Prevention. Preventing lead poisoning in young children: a statement by the Centers for Disease Control: October 1991. Atlanta: US Department of Health and Human Services; 1991. Schlenker TL, Fritz CJ, Mark D, et al. Screening for pediatric lead poisoning: comparability of simultaneously drawn capillary and venous blood samples. JAMA 1994;271:1346-8. Centers for Disease Control and Prevention. Screening young children for lead poisoning: guidance for state and local public health officials. November 1997. Harvey B. New lead screening guidelines from the Centers for Disease Control and Prevention: how will they affect pediatricians? Pediatrics 1997;100:384-8. Annest JL. Trends in the blood lead levels of the US population. In: Rutter M, Jones RR, editors. Lead versus health. Chichester and New York: John Wiley and Sons; 1983. p. 33-58.

25