sign in sign up
<<
Home , Gastrointestinal tract

Raman Sreedharan, MD*, and Devendra I. Mehta, MD‡

ABSTRACT. The developing gastrointestinal tract maturation. In addition to recognized environmental from conception to adolescence is in constant direct in- toxic agents, in this rapidly changing world, the ar- teraction with an increasingly complex environment. ray of novel toxins that make their way into the GI This sets up the potential for unrecognized acute as well tract poses significant threats and needs to be better as chronic disorders, some of which may be difficult to understood. pinpoint in a developing infant and child, given the wide variations that exist. It is startling to note how early some environmental toxins can come into contact with the ROUTES OF ENTRY developing , where vulnerability may be height- ened and maturation of detoxifying pathways may be Environmental toxins taken orally may be modi- incomplete. Although the complex process of recogniz- fied in the GI tract by gastric pH, digestive , ing, detoxifying, and avoiding the toxic substance by the or even that live in the intestines. Environ- body has presumably evolved over a substantial period mental toxins that are internalized by absorp- of time, in this rapidly changing world, the array of novel tion or by may be secreted into the toxins that make their way into the gastrointestinal tract through the biliary system and lead to toxicity. Also, is increasing. There remain many gaps in understanding toxins suspended in air make their way into the the effects of environmental toxins on all of the devel- opmental stages from conception to adolescence. Al- intestinal tract by drainage from the sinuses into the though threshold levels have typically been derived from and . adult or data, factors such as size, relative differ- ences in consumption in proportion to size especially in infancy, and variable physiologic maturation of meta- Mucosal Factors bolic pathways are not well understood. The vulnerabil- A thin preepithelial water layer (“unstirred water ity may be further accentuated by physical factors that layer”) and a mucous layer cover the intestinal mu- alter with maturity, such as permeability and critical cosa and limit absorption to toxins that can diffuse. times during organogenesis or maturation. Also of Lipid solubility will increase the absorption, as will concern is how little is known about low-dose, long-term smaller particle size. The intestinal luminal pH plays exposure, as well as any interplay with common ill- nesses. This article focuses on environmental toxins that a role by altering the ionization of molecules so that have been shown to have toxic effects on the gastrointes- nonionized forms of the weak bases and acids are tinal tract. Pediatrics 2004;113:1044–1050; development, absorbed more rapidly than the ionized forms. The intestinal mucosa, toxins. mucous binding and absorption of metals such as cobalt, , lead, and are pH dependent. The rapid turnover of the intestinal mucosa helps ABBREVIATIONS. GI, gastrointestinal; CYP, cytochrome P450. to protect the mucosa and the body against toxic injuries. The regenerative capacity after injury and he gastrointestinal (GI) tract, like the skin and damage are remarkable because of the mucosa’s ca- the , is in constant direct pacity for rapid turnover and has been studied ex- Tinteraction with the environment. The func- tensively with the dog after interruption of tions of the GI tract as a protective barrier are as blood supply. The lower two thirds of the crypts important as its functions of and absorp- form the proliferative compartment of the mucosa tion but vary with age and maturity. The large sur- and, because of their location, are protected from the face area and prolonged exposure time increase risk reach of toxic substances. This could explain the low of toxin-mediated damage, and increased permeabil- incidence of small intestinal carcinoma despite its ity in early infancy may augment this further. Com- large area. The presence of cytotoxic substances stim- plex processes of recognizing, detoxifying, and ulates exfoliation of the cells into the lumen. Also, avoiding toxic substances also undergo physiologic studies have demonstrated that during the periods of cytotoxic exposure, glucose absorption and

From the *Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; activities are decreased. and ‡Nemours Children’s Clinic, Wilmington, Alfred I. duPont Hospital for Children, Wilmington, Delaware. Received for publication Oct 7, 2003; accepted Oct 20, 2003. Detoxification Reprint requests to (D.I.M.) Division of , NCC-Wilming- The detoxification mechanism that exists in the ton, Alfred I. duPont Hospital for Children, Box 269, Wilmington, DE 19899. intestinal mucosa serves as a second-line barrier and E-mail: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Acad- has been studied well in animal models and also to emy of Pediatrics. an extent in . Regional differences are also

1044 PEDIATRICS Vol. 113Downloaded No. 4 April from www.aappublications.org/news 2004 by guest on October 2, 2021 noted, with most enzymes diminishing in expression DIFFERENTIAL VULNERABILITIES AND CRITICAL in distal small bowel. Studies conducted in rat small WINDOWS OF EXPOSURE OF THE GI TRACT: intestines have shown that cytochrome P450 (CYP), FROM CONCEPTION TO ADOLESCENCE NADPH-CYP reductase, p-nitroansole o-demethyl- ase, and benzpyrene hydroxylase activities are ex- Antenatal pressed 3 to 10 times more in the upper villous cells Maternal diet is the major factor governing expo- of the proximal small bowel.1 This may represent an sure at conception and in utero. The rapidly growing evolutionary adaptation as the highest concentra- is susceptible, but the acts as barrier. tions of environmental toxins are presented to the Although transplacental transport of environmental upper small bowel. toxins, such as lead and mercury, is recognized, tox- Pharmacokinetic differences may play a part in the ins in amniotic fluid, such as nicotine and cotinin, have been poorly studied for possible absorption by age-related differences in the incidence of adverse 7 effects of environmental toxins. Phase I reactions either the skin or the GI tract. Specific GI effects of depend predominantly on CYP enzymes, particu- maternal are cleft and and post- natal growth retardation. larly as most are lipophilic. Specific CYP en- zymes are developmentally regulated and affect pro- Postnatal Changes duction of metabolites, including possibly toxic ones, The postnatal maturing GI tract undergoes several as well as efficacy of therapy. Thus, CYP2D6 Ͻ changes that may significantly alter risk of toxicity activity is 1% of the adult level and remains low (Table 1). Changes in vulnerability to toxins as a until after 28 days of age. Drugs that use these path- ␤ result of many of these factors have largely been ways, such as -blockers and tricyclic antidepres- studied only in animal models and may not be ap- sants, could result in toxicity, including anticholin- plicable. Mucosal permeability to macromolecules 2 ergic gastrointestinal side effects. Conversely, diminishes in the first few days of life in humans but CYP3A, used to metabolize a large number of drugs, diminishes much later in . In addition, influ- is present in significant amounts in the fetal . ence of GI disease, more common in infancy and Extraintestinal CYP3A may be the most important early childhood, may alter absorption by changes in enzyme for orally administered drugs, although the , mucosal integrity, or surface area. Lead ontogeny has not been evaluated.3 Indeed, the activ- (Table 2) and cadmium absorption is markedly in- ity of these enzymes is greater in infants and children creased in early childhood. Absorption of both met- compared with adolescents and adults. In children, als increases in states as the number CYP-catalyzed is increased, and uridine of carriers shared by all 3 metals increases in the diphosphate-glucuronosyltransferase–catalyzed me- .8 tabolism is not significantly different from that in Low production in infants may lead to adults.4 increased small bowel bacterial overgrowth. Methe- Phase II enzymes also show developmental regu- moglobinemia in infants may have resulted from lation that affect . N acetyl trans- conversion of nitrate from contaminated well water ferase 2 activity is low in infants and children to nitrite.9 younger than 3 years, essentially making them phe- The disposition of drugs and other environmental notypically resemble slow metabolizers. By extrapo- toxins varies at different stages of child develop- lation, slow metabolizers are at greater risk of toxic- ment. Generally, absorption is slower in younger ity, including toxic epidermal necrolysis and children. The extracellular volume is higher, and the Stevens-Johnson syndrome.5 In contrast, higher red extent of binding is lower. Renal excretion is blood cell thiopurine methyltransferase activity ob- lower, and environmental toxin metabolic pathways served in newborn infants may have therapeutic im- that depend on activity in the liver may increase concentration of toxins. Animal studies plications in terms of levels of azathioprine and show diminished or absent , reductase, or 6-mercaptopurine and hence efficacy and toxicity, demethylase activity at birth in the rabbit and lack of but no data to date indicate how long this higher 6 uridine diphosphate–glucuronyl transferase in the activity is maintained. In general, pharmacokinetic guinea but not in the rabbit.10 Interspecies differ- studies in infants and children have been used to ences highlight the dangers of extrapolation to hu- provide inferential information on the impact of de- mans. velopment on the activity of drug-metabolizing en- zymes. Because different pathways often metabolize TABLE 1. Age-Dependent Changes in Gastrointestinal Func- these drugs, the information obtained provides only tions an overview. In some cases, these enzyme systems may instead activate toxins, such as carbon tetrachlo- GI Segment Function Changes in Children ride, which then dissociates into toxic free radicals in Gastric pH Decreased in neonates the lumen. Finally, the different processes involved Gastric transit time Prolonged Small bowel Mucosal blood perfusion Varying in absorption, such as diffusion, nonionic diffusion, Mucosal surface Increased facilitated diffusion, specific active transport, and Permeability Increased in neonates toxins, might usurp solvent drag, and mechanisms to Intestinal flora Digestion/nutrients Increased counter these with respect to a particular toxin may Digestive enzymes Decreased in infancy be useful therapeutically. Modified from Schumann et al.8

Downloaded from www.aappublications.org/news by guest on October 2, 2021 SUPPLEMENT 1045 TABLE 2. Some Specific Environmental Toxins Toxin Sources GI Manifestations Age-Related Factors, Normal Ranges, and Other Diagnostic Clues Aluminum , binder in . There are very few acute Infants and premature infants are at fluid, deodorants, cooking vessels, manifestations. increased risk because of immature foils of food wrap, aircraft and renal function. Patients with renal automobile industry. impairment are more susceptible for toxicity. , deranged metabolism, and encephalopathy are the systemic features. Normal serum level is 0.35–0.85 ␮g/dL and for patients on aluminum is Ͻ3 ␮g/dL. Arsenic Chemotherapeutic agent, insecticide, Arsenic is a GI irritant and produces Multisystem involvement should algaecide, rat , Grant’s ant necrosis and ulceration. A/c arouse suspicion. Clinical killer, Fowler’s and poisoning (exposure Ͻ7 days) examination looking for Mees’ homeopathic . Naturally gives a metallic in the lines, anemia, and prolonged QTc contaminated underground water and followed by on ECG. Blood levels are reliable in India and Bangladesh,12,13 beer nausea, and “rice water” only if done within 4 h after poisoning epidemic in England,14 . Subacute poisoning . Urine level is a good and the infant formula (exposure lasting 7 days to 1 indicator of recent exposure. Hair contamination in Japan are month) gives rise to persistent and nail levels are used for epidemics related to arsenic toxicity. vomiting, diarrhea, and abdominal detecting past exposure. pain. In c/c poisoning (exposure Abdominal radiographs after Ͼ1 month), the GI manifestations ingestion may be helpful as arsenic are few and is one of is radio-opaque. Normal range in them. blood is 0.2–6.2 ␮g/dL and in urine is 5–50 ␮g/day. Boric acid Antiseptics, insecticides that kill Easily absorbed through mucous Multisystem effects include CNS, cockroaches. membrane. Produces intense renal, hepatic, and mucosal erythroderma described involvement. Age-dependent as “boiled lobster appearance.”15–17 vulnerability has been noted with Nausea and blue-green vomit maximum toxicity in infants. The followed by diarrhea are the GI levels do not correlate well with manifestations. the toxic effects. Accepted pediatric blood level is Ͻ7 mg/dL and for adults Ͻ2 mg/L Copper Contaminated water, cooking utensils, A/c toxicity–nausea, vomiting and Indian childhood and Bordeaux mixture (pesticide). irritation of the GI tract producing German childhood cirrhosis hemorrhagic . C/c develop as a result of the toxicity usually manifests as liver immaturity of the biliary copper and CNS dysfunction as these are excretory mechanism in children. the target organs. WHO recommended daily requirement of copper is 2 mg. EPA recommended level in drinking water is Ͻ1 mg/L. Cadmium Cadmium-plated food containers, A/c toxicity presents as gastro- Yellow ring at the of galvanized water pipes, batteries, with vomiting, diarrhea, teeth as a result of cadmium radiation screens, plastic, cigarette and colicky . sulfide. Accumulation is highest in smoke. Destroys structure of the first3yoflife. Animal studies mucosa and inhibits absorption of have reported teratogenic effect phosphorous and proteins and with chronic exposure to some enzymes, eg, contaminated water. Normal carboxypeptidases. blood level range between 0.1 and 0.5 ␮g/dL. Formaldehyde Used as disinfectant and Ingestion produces nausea, Respiratory symptoms as a result of fixative (formalin). Component of abdominal pain, vomiting, and inhalation are usually a feature. cigarette smoke. Also used in glue, diarrhea. Can produce coagulation Environmental agency estimates textile and plastic industries. necrosis of distal esophagus and mean home level to be ϳ0.03 stomach with complications of ppm.18 Normal blood level range bleeding, perforation metabolic is 0.6–4.0 mg/L. Glutaraldehyde, derangement, , and death. which is very similar in chemical Stricture is a chronic complication. nature (used in Cidex), has been known to produce after using colonoscopes cleaned with glutaraldehyde.19,20 peroxide Used as a disinfectant. Industrial Ingestion produces vomiting, pain, Toxicity is attributable to direct exposure from textile, bleach, paper, and . oxidation and is concentration and rocket fuel industries. is pale and at times erythematous. dependent; 1 mL of 3% hydrogen Gastric mucosal edema and peroxide can liberate 10 mL of mucosal hemorrhage produces oxygen and produces the toxic hemetemesis.21 necrosis, effects and distension and may mesenteric embolization, and lead to air embolism. Radiography portal and hepatic venous gas can detect air emboli in the gut. have been reported.22, 23

1046 GASTROINTESTINALDownloaded TRACT from www.aappublications.org/news by guest on October 2, 2021 TABLE 2. Continued Toxin Sources GI Manifestations Age-Related Factors, Normal Ranges, and Other Diagnostic Clues Hypochlorite Deodorizers, bleaches, and water Depending on dilution of solution Respiratory manifestations, dermal purifiers. and duration of exposure, varied toxicity, electrolyte imbalances, effects from mild irritation to hemolysis, and cardiac arrest are superficial buccal to associated complications. intestinal strictures. Iodides Disinfectants (Betadine), Irritation and ulceration of Multisystem involvement involving expectorants, contrast material in intestinal mucosa. Chronic , renal, and respiratory radiography, Lugol’s iodine toxicity can lead to painful systems. Lab tests may give an (treatment of ), enlargement of the salivary erroneously high level of chloride and vaginal irrigants. . because the auto-analyzers read the iodide as chloride. Negative can give a clue to diagnosis. Serum levels help in the formulation of management protocols. Iron Iron tablets, multivitamins. There are 5 stages described in iron This is the most common cause of poisoning24 of which stage 1 and death as a result of poisoning in stage 5 have predominantly GI children.25 In iron overdosage in features. Stage 1 symptoms , the fetus is naturally include vomiting, abdominal protected from iron toxicity pain, diarrhea, and GI because transplacental iron hemorrhage. Stage 2 has few GI transport is an active saturable symptoms followed by stages 3 process. Radiographs of the and 4, which comprises the abdomen can be helpful during acidosis, shock, and liver acute poisoning as a result of necrosis phase. Stage 5, which ingestion. Normal blood levels: occurs 4–5 wk after the initial newborns 100–250 ␮g/dL, ingestion, has features of infants 40–100 ␮g/dL, pediatric intestinal obstruction as a result 50–120 ␮g/dL. of stricture formation, the most common site being the gastric outlet. Lead Storage batteries, soldering A/c toxicity follows accidental Young children have 4–5 times materials, automobile industry, ingestion, and the features more absorption capacity for as antiknock agent in petrol, lead- include abdominal cramps and lead compared with adults. glazed crockery, lead-soldered pain, which is referred to as Absorption is increased in iron cans, lead-soldered electric coils “lead colic.” Constipation is deficiency states. Normal blood in heaters for water or usually a feature for both a/c levels Ͻ10 ␮g/dL. food and cosmetics. and c/c poisoning, but diarrhea may occur. “Lead lines” as a result of deposition of lead sulfide in the gingival margins is a feature of c/c toxicity.26 Mercury Mercury-contaminated food Inorganic mercury produces the Methyl mercury crosses the (Minamata disease in Japan as a most GI symptoms, which placenta easily and reaches high result of contamination of and include nausea, vomiting, levels in the cord blood and food grain contamination in Iraq), abdominal pain, and life- produces a variety of congenital pink disease or acrodynia threatening mucosal erosions anomalies, including described from England as a leading to hemetemesis. microcephaly, mental retardation, result of calomel teething Elemental mercury is usually not and motor deficits. Normal .27 harmful except if it is trapped in levels: blood Ͻ1 ␮g/dL and or when it is urine Ͻ2 ␮g/dL. Spot urine tests converted by bacteria to organic available for rapid detection. mercury and is absorbed.28–30 Abdominal X-ray for detection of Chronic elemental mercury mercury in gut. poisoning gives rise to gingivitis, chelitis, and stomatitis. Nickel Water contamination with the water- Large quantities when ingested Nickel intake normally varies from soluble nickel sulfate and nickel produces nausea and vomiting, 150–700 ␮g/day. Doses Ͼ250 chloride. Industrial uses in steel, abdominal cramping, and ␮g/g of diet was toxic in animal gasoline, batteries, plastic, and diarrhea. studies, and human studies galvanization. showed oral doses up to 18 ␮g/kg body weight did not produce any adverse effects. Normal level: 0.11–0.46 ␮g/dL. Plutonium Nuclear power plants, nuclear Stomach and colon . The ICPR max tolerable dose is 300 weapons. 50%–75% of aerosol form of Becquerel. Intestinal absorption is plutonium is cleared form the increased by a factor of 100 in into the GI tract by ciliary infants. movement.

Downloaded from www.aappublications.org/news by guest on October 2, 2021 SUPPLEMENT 1047 TABLE 2. Continued Toxin Sources GI Manifestations Age-Related Factors, Normal Ranges, and Other Diagnostic Clues Thallium Rhodenticide, pesticide, Nausea, vomiting, and diarrhea. Symptoms are dose related. semiconductor industry, Paralytic , , Neurologic manifestations are the pyrotechny, thermometer and constipation have been hallmark of the disease. Also industry, cardiac scanning. reported. Parotid , dermatologic manifestations and pancreas, and liver sudden cardiac death as a result involvement also are of autonomic disturbances can documented. occur as late manifestations. Normal blood range: 0.5 ␮g/dL. Tin Food stored in tin containers, Inorganic form of tin: a/c Toxic effects with food containing antiseptics, fungicides, insecticide, toxicity is rare and c/c Ͼ1400 ppm of tin. Age- and molluscacide. Occupational toxicity is unknown. Organic dependent vulnerabilities have exposure in polyvinyl chloride, form of tin: pancreatic and not been studied. silicon, and polyurethane liver dysfunction. industries. ECG indicates echocardiogram; CNS, central ; WHO, World Health Organization; EPA, Environmental Protection Agency; ICPR, International Committee on Radiological Protection.

Infancy Adolescence Maternal diet remains an important source of en- Risk-taking behaviors such as smoking, ingestion vironmental toxins in breastfed infants. Many envi- of intoxicants, or part-time manual jobs affect expo- ronmental toxins, including halogenated pesticides sure to environmental toxins. Smoking is a risk factor such as polychlorinated biphenyls and dioxins, may for disease. Hormonal changes lead to be concentrated significantly in the fat. Because growth and differentiation of tissues, making these milk is typically the main diet, constant exposure more vulnerable to toxins. A change in the metabolic over several months may occur. Currently, however, rate of environmental toxins pathways occurs, lead- there is no evidence that these concentrations reach ing to reduced CYP expression, and theophylline thresholds that are harmful, and milk is still metabolism decreases to adult levels. recommended by the American Academy of Pediat- rics as the best choice. Milk formulas from cow milk Specific Environmental Toxins may be less concentrated, especially as the fat source Minor GI symptoms are common in many toxic is nondairy. However, possible risks of other con- exposures, although other organs may be more in- taminants such as warrant additional volved. In Table 2, environmental toxins for which study, as the amounts ingested are large over a sus- GI symptoms either are common or may be the major tained period of months. presenting signs are listed. Age-specific features are noted. In Table 3, some biological toxins for which GI Childhood symptoms predominate are listed. Several environmental factors affect exposure to toxins in childhood. Household and liquids CHILDHOOD GI DISORDERS FOR WHICH may be ingested and lead to caustic esophageal in- ENVIRONMENTAL TOXINS MAY BE CONSIDERED juries. These injuries markedly increase the risk of Acute exposures may lead to nausea, vomiting, in later life.11 Toxic plants, such as and diarrhea and may be difficult to identify, as Dieffenbachia, including mother-in-law’s and infectious causes are more common. However, addi- berries such as holly berries (Table 3), can lead to tional features, such as excessive drowsiness, involv- severe oral and GI disturbances and are most com- ing other organs should raise suspicion. Gingivitis, mon in childhood. Schools, child care facilities, and edema, and erythema of ; dysphagia; playgrounds expose children to a wide array of en- and GI hemorrhage also may suggest environmental vironmental toxins ranging from lead to herbicides, toxin exposure, especially heavy metals. Copper, heavy metals, and pesticides. Outdoor play areas pokeweed, and toxalbumins may lead to bloody di- such as wooden playground equipment may be a arrhea, mimicking acute colitis. Indeed, in inflamma- source of arsenic or chromium if ingested. tory bowel disease, environmental toxins such as A child’s diet is typically less varied than in ado- ultrafine particles of titanium oxide have been pos- lescents or adults but may contain proportionally tulated as causes.46 more fruits and vegetables. This exposes them to greater amounts of pesticides. Common childhood CONCLUSION disorders, such as constipation, may significantly in- Changes in diet and exposure to environmental crease toxin absorption because of delayed transit toxins vary tremendously with age. Developmental time. stages of protective mechanisms such as mucosal The environmental toxin metabolic pathways con- permeability also lead to age-specific risks. Although tinue to change, as exemplified by peak theophylline many gaps in understanding effects of environmen- metabolism occurring at this age and leading to dif- tal toxins on all of the developmental stages from ferent urinary metabolite levels than in infancy. conception to adolescence remain, it is clear that the

1048 GASTROINTESTINALDownloaded TRACT from www.aappublications.org/news by guest on October 2, 2021 TABLE 3. Some Specific Biological Toxins Toxin Sources GI Manifestations Age-Related Factors, Normal Ranges, and Othe Diagnostic Clues Clostridium botulinum, a spore- Infant botulism: incubation Children Ͻ1 year are most forming obligate anaerobic period is unknown. susceptible. Factors that bacterium, produces the toxin. Constipation precedes increase susceptibility include The sources are canned food, drooling, feeding difficulty, breast feeding, , honey, corn , etc.31,32 weak cry, ptosis, and muscle GI tract , and weakness. There is loss of inflammatory bowel disease. tone of the anal sphincter. Diagnosis: toxin in serum, Foodborne Botulism can be stool, and food is detected by abrupt in onset or can toxin neutralization bioassay evolve gradually over in mice. Anaerobic culture of several days. Nausea, food items, stool, or rectal vomiting, and diarrhea are washings and gastric aspirate early features, and for Clostridium botulinum is constipation is a late feature. diagnostic. If stool collection is There is feeding difficulty as difficult as a result of a result of dry mouth, constipation, then sterile dysphagia, and bulbar nonbacteriostatic water is used paralysis. Descending as to get sample. symmetrical paralysis follows. Pokeweed (also known as Phytolacca americana is a large Is a potent GI mucosal irritant. Symptoms usually self-resolve in poke, poke berry, and shrub-like herb with berries. The Produces bitter taste in 24 h. The toxins are ink berry). leaves are eaten as cooked mouth followed by nausea, phytolaccine and pokeweed greens and in salads. vomiting, and cramping mitogen, which are found in abdominal pain. May also all parts of the plant with the lead to foamy stools and highest concentration in the bloody diarrhea. roots and least in the berries.33 Ingestion of few berries usually does not cause any problems. Repeated boiling and discarding the water will make the plant less toxic.34 Holly berries Shrubs with green serrated leaves Ingestion of berries produces Poisoning is usually seen during and red berries. nausea, vomiting, crampy winter, as the berries of this abdominal pain, and plant turn red and pretty and diarrhea.35 so is used for decorations. Arum family Attractive indoor plants with Immediate local pain followed The insoluble calcium oxalate calcium oxalate crystals in all by edema. Gives a sensation crystals arranged as raphide parts of the plants. like “chewing on pins or gives rise to local pain and glass.” Rarely produces other symptoms by triggering mucosal ulcerations and and bradykinin airway obstruction.36 release.37 Symptoms usually resolve spontaneously in a few hours.38 Solanaceous alkaloids Jerusalem cherry S pseudocapsicum), The toxin is a glycoalkaloid, Ripe fruits are less toxic than potato (S tuberosum), common which is an irritant to the unripe fruits.39,40 Multisystem night shade (S nigra), and woody mucosa producing vomiting effects including some night shade (S dulcamara). and diarrhea within hours effects and Ingestion of berries, fruits, and of ingestion. It is death have been reported.40–42 potato sprouts or potato source systemically absorbed after of toxicity.39,40 hydrolysis in the stomach. Toxalbumins The plants Ricinus communis Symptoms usually develop Multisystem failure and death (castor seed) produce the within 2–10 h after are complications.44 Most toxalbumin ricin, and Abrus ingestion, but delayed exposures result in limited precatorius (rosary pea) effects have been reported.43 gastroenteritis with minimal produces the toxalbumin . Usually presents as colicky systemic features because the The seeds of both of these plants abdominal pain followed by toxin is released only if the are attractive and are used for bouts of vomiting and seeds’ hard shell is broken, making rosaries and necklaces. diarrhea, which may and most children do not have become bloody. the chewing strength to do this.45 various age groups need to be considered separately. need to be studied, and the impact of common ill- The GI tract, despite being an important detoxifica- nesses on toxicity needs to be evaluated. Further- tion site, is also vulnerable because of its specific more, although safe threshold levels have been de- features that allow optimal digestion and absorption. rived from adult or animal data, factors such as size, The vulnerability is further accentuated by develop- relative differences in consumption, and different mental factors such as permeability and the critical maturity of metabolic pathways suggest that these timing for many target organs. Low dose, long-term could be misleading. Little is known about specific exposure and high-dose, short-term exposure both changes and risks during adolescence, and caution

Downloaded from www.aappublications.org/news by guest on October 2, 2021 SUPPLEMENT 1049 should be used when applying adult-based thresh- Near fatal hydrogen peroxide ingestion. Ann Emerg Med. 1989;18: old values. 778–779 22. Luu TA, Kelley MT, Strauch JA, Avradopoulos K. Portal gas embolism from hydrogen peroxide ingestion. Ann Emerg Med. 1992;21: REFERENCES 1391–1393 1. Hoensch H, Woo CH, Raffin SB, Schmid R. Oxidative metabolism of 23. Rackoff WR, Merton DF. Gas embolization after ingestion of hydrogen foreign compounds in rat : cellular localization and de- peroxide. Pediatrics. 1990;85:593–594 pendence on dietary iron. Gastroenterology. 1976;70:1063–1070 24. Banner W Jr, Tong TG. Iron poisoning. Pediatr Clin North Am. 1986;33: 2. Nemeroff CB, DeVane CL, Pollock BG. Newer and the 393–409 cytochrome P450 system. Am J Psychiatry. 1996;153:311–320 25. Litovitz T, Manoguerra A. Comparison of pediatric poisoning hazards: 3. Paine MF, Shen DD, Kunze KL, et al. First-pass metabolism of midazo- an analysis of 38 million exposure incidents. Pediatrics. 1992;89:999–1006 lam by the human intestine. Clin Pharmacol Ther. 1996;60:14–24 26. Bruggenkate CM, Lopes Cardozo E, Maaskant P, van der Waal I. Lead 4. Anderson GD. Children versus adults: pharmacokinetic and adverse- poisoning with pigmentation of the oral mucosa. Oral Surg. 1975;39: effect differences. Epilepsia. 2002;43(suppl 3):53–59 747–753 5. May DG. Genetic differences in drug disposition. J Clin Pharmacol. 27. Troen P, Kaufman SA, Katz KH. Mercuric bichloride poisoning. N Engl 1994;34:881–897 J Med. 1951;244–259 6. McLeod HL, Krynetski EY, Wilimas JA, Evans WE. Higher activity of 28. Canady R, Rabe CS, Gan K. Toxicological profile for mercury. Atlanta, polymorphic thiopurine S-methyltransferase in erythrocytes from neo- GA: Department of Public Health Service; 1994:66–259 nates compared to adults. Pharmacogenetics. 1995;5:281–286 29. Bredfeldt JE, Moeller DD. Systemic mercury intoxication following 7. Van Vunakis H, Langone JJ, Milunsky A. Nicotine and cotinin in the rupture of a Miller-Abbott tube. Am J Gastroenterol. 1978;69:478–480 amniotic fluid of smokers in the second trimester of pregnancy. Am J 30. Mayer O, Cantor MD. Mercury lost in the gastrointestinal tract. JAMA. Obstet Gynecol. 1974;20:64–66 1951;146–560 8. Schumann K, Elsenhans B, Richter E. Gastrointestinal tract. In: Mar- 31. Spika JS, Shaffner N, Hargrett-Bean N, et al. Risk factors for infant quardt H, Schafer SG, McClellan R, Welsch F, eds. Toxicology. San botulism in the United States. Am J Dis Child. 1989;143:828–832 Diego, CA: Academic Press; 1999:573–585 32. Kothare SV, Kassner EG. Infant botulism: a rare cause of colonic ileus. 9. Luyens JN. The legacy of well-water methemoglobinemia. JAMA. 1987; Pediatr Radiol. 1995;25:24–26 257:2793–2795 33. Litovitz TL, Klein-Schwartz W, Dyer KS, et al. 1997 annual report of the 10. Lucier GW, Sonawane BR, McDaniel OS. Glucuronidation and deglu- American Association of Poison Control Centers Toxic Exposure Sur- curonidation reactions in hepatic and extrahepatic tissues during peri- veillance System. Am J Emerg Med. 1998;16:443–497 natal development. Drug Metab Dispos. 1977;5:279–287 34. Roberge R, Brader E, Martin ML, et al. The root of evil—pokeweed 11. Appleqaist P, Salno M. Lye corrosion carcinoma of the esophagus: a intoxication. Ann Emerg Med. 1986;15:470–473 review of 63 cases. Cancer. 1980;45:2655 35. Rodriques TD, Johnson PN, Jefferey LP. Holly berry ingestion: case 12. Rahman M, Tondel M, Ahmed SA, Chowchury IA, Faruquee MH, report. Vet Hum Toxicol. 1984;26:157–180 Axelson O. Hypertension and arsenic exposure in Bangladesh. Hyper- 36. Evans CRH. Oral ulceration after contact with the houseplant Dieffen- tension. 1999;33:74–78 bachia. Br Dent J. 1987;162:467–468 13. Subramanian KS, Kosnett MJ. Human exposure to arsenic from con- 37. Rauber A. Observation on the idioblasts of Dieffenbachia. J Toxicol Clin sumption of well water in West Bengal, India. Int J Occup Environ Health. 1998;4:217–230 Toxicol. 1985;23:79 14. Keynack TN, Kirby W, et al. Arsenical poisoning from beer drinking. 38. Mrvos R, Dean BS, Krenzelok EP. Philodendron/Dieffenbachia Lancet. 1900:1600–1603 ingestion: are they a problem? J Toxicol Clin Toxicol. 1991;29:485–491 15. Wong LC, Heimbach, Trucott DR, Duncan BD. Boric acid poisoning: 39. Dalvi RR. Toxicology of solanine: an overview. Vet Hum Toxicol. 1983; report of 11 cases. Can Med Assoc J. 1964;90:1018–1023 25:13–15 16. Restuccio A, Mortensen ME, Kelly MT. Fatal ingestion of boric acid in 40. Hornfeldt CS, Collins JE. Toxicity of nightshade berries (Solanum dul- an adult. Am J Emerg Med. 1992;10:545–547 camara) in mice. J Toxicol Clin Toxicol. 1990;28:185–192 17. Rubenstein AD, Mushner DM. Epidemic boric acid poisoning simulat- 41. McMillan M, Thompson JC. An outbreak of suspected solanine poison- ing staphylococcal toxic epidermal necrolysis of the newborn infant: ing in schoolboys. Q J Med. 1979;48:227–243 Ritters disease. J Pediatr. 1970; 884–887 42. Nishie K, Gumbmann MR, Keyl AC. of solanine. Toxicol 18. Imbus HR. Clinical evaluation of patients with complaints related to Appl Pharmacol. 1971;19:81–92 formaldehyde exposure. J Clin Immunol. 1985;76:831–840 43. Schneider SM. Toxic plant ingestions: optimizing the course of treat- 19. Durante L, Zulty JC, Israel E, et al. Investigation of an outbreak of ment. Emerg Med Rep. 1992;13:141–142 bloody diarrhea: association with endoscopic cleaning solution and 44. Balint GA. Ricin: the toxic protein of castor oil seeds. Toxicology. 1974; demonstration of lesions in an animal model. Am J Med. 1992;92: 2:77–102 476–480 45. Challoner KR, McCarron MM. Castor bean intoxication. Ann Emerg 20. West AB, Kuan SF, Bennick M, Lagarde S. Glutaraldehyde colitis fol- Med. 1990;19:1177–1183 lowing : clinical and pathological features and investigation 46. Powell JJ, Harvey RS, Ashwood P, et al. Immune potentiation of ultra- of an outbreak. Gastroenterology. 1995;108:1250–1255 fine dietary particles in normal subjects and patients with inflammatory 21. Giberson TP, Kern JD, Pettigrew DW 3rd, Eaves CC Jr, Haynes JF Jr. bowel disease. J Autoimmun. 2000;14:99–105

1050 GASTROINTESTINALDownloaded TRACT from www.aappublications.org/news by guest on October 2, 2021 Gastrointestinal Tract Raman Sreedharan and Devendra I. Mehta Pediatrics 2004;113;1044

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/113/Supplement_3/1044 References This article cites 40 articles, 4 of which you can access for free at: http://pediatrics.aappublications.org/content/113/Supplement_3/1044 #BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Gastroenterology http://www.aappublications.org/cgi/collection/gastroenterology_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on October 2, 2021 Gastrointestinal Tract Raman Sreedharan and Devendra I. Mehta Pediatrics 2004;113;1044

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/113/Supplement_3/1044

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2004 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Downloaded from www.aappublications.org/news by guest on October 2, 2021