5
Health Effects of Excess Copper

THIS chapter focuses on the health effects associated with acute and chronic exposure to excess copper. Information on those effects comes from human case-reports and population-based studies. The emphasis is placed on acute exposure effects on the gastrointestinal (GI) system. Effects on other target organs, such as the liver, in subjects following high-dose chronic exposure and in sensitive populations are considered. Toxicity data from animal studies are presented, and the use of animal models for studying the mechanism underlying the toxicity of copper in humans is discussed.

ACUTE TOXICITY

Case Reports and Population-Based Studies

Human cases of acute copper toxicosis are presented in this section. The cases are cited in reports by the NRC (1977), EPA (1987), the U.S. Agency for Toxic Substances and Disease Registry (ATSDR 1990), and the World Health Organization's International Programme of Chemical Safety (IPCS 1998). Table 5-1 summarizes the reported health effects of ingested copper in humans. Most human data on high-dose acute poisoning are based on cases of suicidal intent with the ingestion of copper compounds or accidental consumption of copper-contaminated foods and beverages. In such cases, it is difficult to estimate the quantity of copper consumed, whether it was in solid form, aqueous suspension, or solution. It is also



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 78
Copper in Drinking Water 5 Health Effects of Excess Copper THIS chapter focuses on the health effects associated with acute and chronic exposure to excess copper. Information on those effects comes from human case-reports and population-based studies. The emphasis is placed on acute exposure effects on the gastrointestinal (GI) system. Effects on other target organs, such as the liver, in subjects following high-dose chronic exposure and in sensitive populations are considered. Toxicity data from animal studies are presented, and the use of animal models for studying the mechanism underlying the toxicity of copper in humans is discussed. ACUTE TOXICITY Case Reports and Population-Based Studies Human cases of acute copper toxicosis are presented in this section. The cases are cited in reports by the NRC (1977), EPA (1987), the U.S. Agency for Toxic Substances and Disease Registry (ATSDR 1990), and the World Health Organization's International Programme of Chemical Safety (IPCS 1998). Table 5-1 summarizes the reported health effects of ingested copper in humans. Most human data on high-dose acute poisoning are based on cases of suicidal intent with the ingestion of copper compounds or accidental consumption of copper-contaminated foods and beverages. In such cases, it is difficult to estimate the quantity of copper consumed, whether it was in solid form, aqueous suspension, or solution. It is also

OCR for page 78
Copper in Drinking Water TABLE 5-1 Case Reports of Copper Toxicosis Following Oral Exposures of Humans to Copper Salts Reference Sex, Age, Number Exposures Clinical Sequelae and Comments Percival 1784 F, 17 yr, 1 Ingestion of ≈ 100 to 130 g of a pickled vegetable, shown by analysis to be contaminated with Cu Abdominal pain, generalized rash, flatulence, vomiting, diarrhea, cardiac arrhythmia, death on the 8th day post-exposure Griffin 1951 M, adults, 6 Ingestion of coffee brewed with water from a Cu-contaminated, gas-heated boiler Nausea, vomiting, malaise Ross 1955 M F, NS, 12 Stewed apples, cooked in a Cu vessel, were served to 87 adults and 458 children; 3 adults and 9 children developed symptoms Bitter taste, nausea, vomiting, and diarrhea Roberts 1956 M, 24 yr, 1 ≈ 400 g of CuSO4 in water over a 4-mo period (≈ 2 g Cu per day) Abdominal pain, hemolytic anemia Sanghvi et al. 1957 M, 18, 20 yr, 2 Ingestion of CuSO4 (amounts unknown) with suicidal intent Sulfhemoglobinemia, acute renal tubular necrosis, azotemia, anuria, coma, and death Wyllie 1957 F, NR, 15 Contaminated alcohol lemon cocktails from cocktail shakers containing Cu; estimated Cu ingestion, 5–32 mg Weakness, abdominal cramps, headache, nausea, dizziness, vomiting in 10/13 nurses; possible causes, other than Cu, not excluded Semple et al. 1960 M, NR, 18 Contaminated tea (≈ 250 mL) containing Cu at 44 mg/L; tea made with water from a Cu-lined, gas-heated boiler Abdominal pain, vomiting, diarrhea, dizziness, and headache developed in 18 of 150 workers within 10 min after drinking the tea Le Van and Perry 1961 M, NR, NR Unspecified number of men on ship drank Cu-contaminated soft drink (Cu content not stated) from a vending machine Several men developed mild nausea Chowdhury et al. 1961 M F, adults, 20 12 women and 8 men attempted suicide by ingestion of unknown quantities of CuSO4 Epigastric pain, nausea, jaundice, hemolysis, hemoglobinuria, proteinuria, glucosuria, hypotension, tachycardia, stupor; no deaths

OCR for page 78
Copper in Drinking Water Reference Sex, Age, Number Exposures Clinical Sequelae and Comments Ghosh and Aggarwal 1962 M F, children, 32 31 children accidentally ingested unknown amounts of CuSO4; one boy (age 11) given CuSO4 for attempted homicide Vomiting was chief complaint; the victim of attempted homicide developed severe hemolysis Bohré et al. 1965 M, adults, 7 Naval officers consumed coffee prepared with water from a Cu-contaminated electrically heated boiler Nausea, vomiting, malaise, collapse, no deaths Chuttani et al. 1965 M F, 14– 60 yr, 53 Oral ingestion with suicidal intent; estimated 1–30 g of CuSO4 Diarrhea (29%), hemoglobinuria and hematuria (29%), anuria (27%), jaundice (23%), hypotension (8%), coma (8%), death (15%) Fairbanks 1967 F, 22 yr, 1 Accidental ingestion of unknown amount of CuSO4 solution Nausea, vomiting, diarrhea, abdominal pain, icterus, melena, hemoglobinuria, proteinuria, mild anemia Wahal et al. 1965 M F, 15– 58 yr, 100 100 patients ingested CuSO4 (dose unknown, mostly suicidal) Hepatotoxicity (36%), renal toxicity (18%), cardiovascular toxicity (10%), neurotoxicity (10%), GI hemorrhage (6%), death (10%) Nicholas 1968 M, NR, 20 Contaminated tea (≈ 250 mL) containing Cu at >30 mg/L; tea made with water from a Cu-lined boiler Diarrhea, nausea, vomiting Singh and Singh 1968 M F, 13– 85 yr, 40 27 males and 13 females; accidental or suicidal ingestion of copper salts Variable hypercupremia, transaminasemia, hyperbilirubinemia, and renal insufficiency; 4 deaths Salmon and Wright 1971 M, 1.25 hr, 1 Oral ingestion of drinking water (Cu at 0.35–0.79 mg/L) over a 3-mo period Prostration, vomiting, red extremities, hypotonia, photophobia, peripheral edema, hypercupremia

OCR for page 78
Copper in Drinking Water Reference Sex, Age, Number Exposures Clinical Sequelae and Comments McMullen 1971 M, NR, ≥ 10 Oral ingestion of Cu-contaminated orange- or lime-flavored soft drinks, dispensed through Cu-containing bottle pourers; drinks contained Cu at 190 and 220 mg/L. At least 10 members of a sports club vomited immediately after consuming the soft drinks Mittal 1972 M, 22 yr, 1 Oral ingestion of ≈ 175 g of CuSO4 (≈ 70 g Cu) Severe abdominal pain, vomiting, diarrhea starting 1.5 hr post- ingestion; renal damage with hemoglobinuria; eventual recovery Chugh et al. 1975 M, 27 yr, 1 Oral ingestion of ≥ 50 g of CuSO4 (≈ 20 g Cu) Cyanosis, oliguria, hemolysis, methemoglobinemia, death 16 hr post-ingestion Agarwal et al. 1975 F, 41 yr, 1 Oral ingestion of CuSO4 with suicidal intent; patient treated by hemodialysis at 13 hr after ingestion Vomiting, diarrhea, hepatorenal failure, coma; hemodialysis was ineffectual; death; autopsy showed Cu in brain, heart, liver, kidney Stein et al. 1976 F, 44 yr, 1 After the patient had ingested ethanol and diazepam, CuSO4 (796 mg Cu) was administered as an emetic Respiratory collapse, massive GI hemorrhage, hemolytic anemia, renal and hepatic failure, death; autopsy showed renal tubular necrosis and increased hepatic Cu content Chugh et al. 1977 M F, 18– 35 yr, 11 Report of 11 cases of acute renal failure in a series of 29 patients with acute CuSO4 poisoning with suicidal intent. Vomiting (100%), epigastric pain (45%), diarrhea (45%), oliguria or anuria (91%), jaundice (91%), coma (18%); death (45%); biopsy or autopsy showed renal tubular necrosis in 7 of 8 patients studied Walsh et al. 1977 M, 1.5 yr, 1 Oral ingestion of 3 g of CuSO4 (≈ 1.2 g Cu) Hemolytic anemia was observed 2 days post-ingestion, with hematuria, glucosuria, proteinuria, cylindruria, hypercupremia, hypercupriuria; recovery period was ≈ 1 yr Stenhammar 1979 ?, 1–2.5 yr, 3 Oral ingestion for unknown duration of tap water containing Cu at 0.22–1 mg/L Prolonged diarrhea with weight loss; symptoms disappeared with change of water source

OCR for page 78
Copper in Drinking Water Reference Sex, Age, Number Exposures Clinical Sequelae and Comments Berg and Lundh 1981 M F, < 3 yr, NR Children at 7 Swedish kindergartens with Cu content in first-draw water from 0.35 to 6.5 mg/L Association noted between Cu content of drinking water and diarrhea, but other possible causes of diarrhea were not studied Spitalny et al. 1984 M F, 5, 7, 32 yr, 3 Oral ingestion of drinking water (Cu at 2–8 mg/L; median 3 mg/L) for 1.5 yr by a family living at the end of a copper water main Episodic nausea, vomiting, abdominal pain occurred 5–20 min after drinking tap water in morning in 3 of 4 family members; the symptoms ceased with change of water source Jantsch et al. 1985 M, 42 yr, 1 Ingestion of ≈ 250 g of CuSO4 (≈ 100 g Cu) in attempted suicide Protracted vomiting, hepatic failure, response to chelation therapy, eventual recovery Müller-Höcker et al. 1988 M F, 1 yr, 2 Two infant siblings consumed for >9 mo Cu-containing tap water (Cu at 2.2–3.4 mg/L); the Cu was derived from Cu pipes Micronodular cirrhosis with hepatic Cu storage, hepatosplenomegaly, jaundice, and hypertransaminasemia; 1 death Knobeloch et al. 1994 M F, NR Five studies of GI upsets associated with ingestion of Cu-containing drinking water Higher incidence of symptoms following ingestion of first-draw water compared with flushed water NR, not recorded      

OCR for page 78
Copper in Drinking Water difficult to control for potential confounding factors, such as microbial agents and their toxins. Following acute ingestion of copper salts (e.g., copper sulfate) in amounts that exceed approximately 1 g, systemic effects are generally observed. The effects include GI mucosal ulcerations and bleeding, acute hemolysis and hemoglobinuria, hepatic necrosis with jaundice, nephropathy with azotemia and oliguria, cardiotoxicity with hypotension, tachyeardia and tachypnea, and central-nervous-system (CNS) manifestations, including dizziness, headache, convulsions, lethargy, stupor, and coma. The systemic sequelae of acute ingestion of copper salts are highly variable. Oral intake of ionic copper usually induces immediate emesis, which reduces the quantity of residual copper available for absorption from the GI tract. Oral intake of copper that is bound to particulates in water or to proteins, lipids, and other constituents of foods is less likely to cause emesis, since the bound forms of copper show reduced bioavailability compared with ionic copper. The principal targets for acute copper toxicosis are the GI, hepatic, renal, hematological, cardiovascular, and CNS systems. There are few, if any, reports of musculoskeletal, dermal, ocular, immunological, carcinogenic, reproductive, or developmental effects in humans following oral ingestion of copper salts, even at high exposure concentrations. Acute copper toxicosis, manifested by hemolysis, headache, febrile reactions, prostration, and GI symptoms, was observed in one child after a solution containing copper sulfate was applied to burned skin during a debridement procedure (Holtzman et al. 1966) and in numerous patients after inadvertent introduction of copper into the circulating blood during hemodialysis (Manzler and Schreiner 1970; CDC 1974; Lyle et al. 1976). In hemodialysis patients, ionic copper can be released from semipermeable membranes fabricated with copper or from copper tubing or heating coils of the dialysis equipment, especially when the dialysate has become acidic (Barbour et al. 1971; Blomfield et al. 1969, 1971; Klein et al. 1972). In two hemodialysis patients, copper intoxication was characterized by marked hemolysis, acidosis, methemoglobinemia, hypoglycemia, vomiting, epigastric pain, diarrhea, and headache, with fatal outcome (Matter et al. 1969). In one report, copper stopcocks in circuits used for exchange transfusions were identified as the source of potentially hazardous infusions of copper in neonates (Blomfield 1969). Administration of copper sulfate as an emetic was identified as another iatrogenic cause of acute copper toxicosis (Holtzman and Haslam 1968). Wyllie (1957) describe one episode of acute GI symptoms associated with a presumed exposure to copper as a result of mixing alcoholic drinks in a copper-contaminated cocktail shaker. In reconstructing the exposure, the author concluded that the lowest adverse effect level was approximately 5.3 mg in 3/4 fluid ounces or 10.65 mg of copper. However, signifi-

OCR for page 78
Copper in Drinking Water cant questions have been raised about the suitability of those data for estimating toxic doses of copper (Donohue 1997). Hopper and Adams (1958) presented five instances where faulty check valves in vending machines were responsible for carbon dioxide back flow and subsequent build-up of copper in vending machine water lines. The first drink in the morning can have a metallic taste, and cause salivation, nausea, vomiting, epigastric burning, or diarrhea (Hopper and Adams 1958). Semple et al. (1960) reported an outbreak of copper poisoning from ingestion of tea that was contaminated with copper sulfate scale deposited in the water used to make the tea. The authors estimated that the total copper in the suspension was 44 mg/L. That estimate is unreliable, however, because exposure likely occurred after a large portion of the scale was dislodged in the vessel, and the water used to make the tea was not available for analysis. The Centers for Disease Control and Prevention (CDC) reported multiple outbreaks of copper poisoning from ingestion of contaminated beverages (CDC 1974, 1975, 1977, 1996). In most cases, the copper concentration associated with illness was in excess of 30 mg/L. A major incident occurred in 1993–1994, where 43 individuals became ill from a single point source in a hotel. Exposures were estimated to range from 4.0 to 70 mg/L. Recurrent GI illness, including nausea and vomiting, occurred in a Vermont family. Exposure was traced to a build-up of copper in the water overnight. Copper concentrations reached 7.8 mg/L (with a range of 2.8 to 7.8 mg/L) (Spitalny et al. 1984). Family members had increased copper concentrations in hair, but not blood. Relief of symptoms occurred when their drinking water was replaced by bottled water. Knobeloch et al. (1994) investigated five individuals who ingested water above EPA's MCLG of 1.3 mg/L and reported abdominal symptoms. The authors suggested that increased copper in tap water can be a relatively common cause of GI symptoms. Using survey methods to gather data on copper-induced illness from soft drinks, Low et al. (1996) queried 2,100 state and local departments of health and agriculture and water utilities. Although the response rate was only 40%, they found 70 incidents of copper poisonings affecting 462 people. Copper concentration data were available for 24 cases and were less than 10 mg/L in 6 of those 24 cases (range of 3.5 to <10 mg/L. Dose estimation from those data is difficult however, because little information is available on the amount of beverage consumed and on whether the drink was consumed with food. Larger epidemiological studies have also investigated the relationship between exposure to excess copper environmentally and occupationally and adverse health effects. Recently, Buchanan et al. (1998) studied

OCR for page 78
Copper in Drinking Water households from lists supplied by the Nebraska Department of Health. Households were chosen on the basis of their drinking-water copper concentrations, which were above 3 mg/L in 60 households, between 2 and 3 mg/L in 60 households, and below 1.3 mg/L in 62 households. A telephone interview was conducted with one adult from each household, addressing the occurrence of GI illness. A nested study was also performed where in-person interviews were conducted and copper water concentrations were measured. The investigators found no association between copper concentration and GI illness. The copper water concentrations ranged from 0.06 to about 5 mg of copper/L in the first draw water. Roberts et al. (1996) examined communities made up of more than 100 people in Delaware. They considered communities in which 10% of the water samples, measured during a statewide survey in 1995, had copper concentrations greater than 5 mg/L. Four communities that met that criteria and one trailer park with older homes and acidic water were studied. First morning tap water was collected, and the households with concentrations in excess of 5 mg/L were revisited for study. Residents were interviewed once per week for 12 weeks and asked about GI symptoms. Although people with high concentrations of copper in their drinking water were slightly more likely to report becoming ill at some point during the study, there was no significant association of tap-water copper concentration and GI symptoms. The committee had difficulty in determining how to use the available epidemiological data. Although copper concentrations were used to stratify exposures in communities, it is difficult to link copper concentrations to individual exposures. Not everyone in a household can drink first-draw water; therefore, the high exposure would be encountered by one person in a household. The epidemiological data provide some assurance that copper concentrations in first-draw water above the current MCLG do not produce a high frequency of adverse GI effects within a community. However, the data do not allow the conclusion that water consumed at those concentrations would not give rise to GI-related symptoms in individuals. As a consequence, the committee relied on experimental studies that involved administration of water containing identified concentrations of copper. In one of the few experimental studies on copper in drinking water, Pizarro et al. (1999) designed a study to determine a threshold concentration for acute GI effects from copper in tap water. Sixty healthy adult women of low socioeconomic status from Santiago, Chile were randomly assigned to groups receiving 1, 3, or 5 mg of copper/L for 2 weeks, followed by 1 week of standard tap water. The women prepared the test water every morning and recorded their water intake and GI symptoms. Daily does of copper were not reported. Nausea, vomiting, abdominal pain or

OCR for page 78
Copper in Drinking Water cramps, diarrhea, and food intolerance were recorded. Of the 60 participants, one woman recorded nausea only and two abdominal pain with 0 mg of copper/L of water. With 1 mg of copper/L, one woman recorded abdominal pain only, two recorded diarrhea only, one recorded diarrhea and vomiting, and one recorded all three symptoms. With 3 mg of copper/L, six women recorded nausea only, three recorded abdominal pain only, and one recorded vomiting only. Four women experienced diarrhea and abdominal pain. At 5 mg of copper/L, nausea only, abdominal pain only, diarrhea only, and vomiting only were recorded by five, two, three, and two women, respectively. One experienced both diarrhea and vomiting at 5 mg of copper/L. Therefore, a total of 21 subjects reported GI problems at some time during the study. Nausea, abdominal pain, or vomiting occurred 5%, 2%, 17%, and 15% of the time at 0, 1, 3 and 5 mg of copper/L, respectively. The data suggest that at or greater than 3 mg of copper/L can be associated with GI effects. The data also indicate a range of sensitivity in the population: 17% of the subjects reported symptoms at 3 mg of copper/L, while 85% did not report symptoms at 5 mg/L. In follow-up to Pizarro et al. (1999), a larger experimental study involving controlled randomized trials (sponsored by the International Copper Association) is being conducted to determine the dose-response relationship more precisely for the GI effects of copper in drinking water (ICA, unpublished material, Oct. 13 1999). The results of that study are nearing completion as this report goes to press. The experimental protocol, methods, and individual data were made available to the committee. The study involved 60 adult volunteers in Ireland (Colerain), Chile (Santiago), and North Dakota (Grand Forks). Each subject drank 200 mL of water containing 0, 2, 4, 6, or 8 mg of copper/L. Symptoms were noted at various times up to 60 rain at each testing center, and a 24-hr follow-up was made for any other symptoms. Each subject received each of the doses in a randomized order once a week. A dose-response for nausea was noted, although a lack of masking for taste might have affected the relationship. Not all individuals noted nausea even at higher doses, and a large variation in sensitivity among subjects is apparent. The fractions of those reporting nausea out of 180 subjects were 8, 7, 11, 25, and 44 at 0, 2, 4, 6, and 8 mg of copper/L of solution, respectively. Those results appear to be consistent with Pizarro et al. (1999), although they were considered too preliminary for further conclusions. An additional study is under way to investigate the acute effects of copper in drinking water. No data are available from that study (L. Chaffin, League of Nebraska Municipalities, personal commun., Feb. 9, 2000). In summary, there are inconsistencies among the data and they suffer from several limitations. There is little information on possible confound-

OCR for page 78
Copper in Drinking Water ers and biases in the studies (including microbial water contamination and water averting behavior of residents), and there is an uneven distribution of risk in multi-member families. Copper concentrations often are not reliable because of a wide variability in first-draw concentrations and samples typically were not collected during the actual study period. Possible acclimatization is also not typically considered. In the experimental and epidemiological studies, sample sizes are small; therefore, the committee is concerned that effects on a sensitive population could have been missed. In addition, little work has addressed the health effects associated with exposure of infants and children to increased concentrations of copper in water. The only experimental study published in the literature indicates that GI symptoms arise from exposure at approximately 3 mg of copper/L (Pizarro et al. 1999). It is important to stress the point that all of the above cases represent acute toxicity as a consequence of the consumption of water or beverages that contain high levels of copper. For systemic effects, doses of copper in water associated with health effects differ from toxic doses in environmental media because of differences in bioavailability among water, food, and other environmental media. Copper ions in water have the highest bioavailability. The bioavailability of copper in the diet is a function of its solubility and also the types of complexes in which it is present. For example, complexes of copper with some amino acids and organic acids result in bioavailability similar to that of soluble copper sulfate (Wapnir 1998), whereas other dietary elements and certain amino acids can inhibit copper absorption. CHRONIC TOXICITY A major target of chronic copper toxicity is the liver. Liver toxicity is usually seen in specific populations, such as individuals with Wilson disease and children with various cirrhosis syndromes (see Chapter 4 for descriptions). However, there has been a case report of chronic ingestion of a high-dose copper supplement (30 mg per day for 2 years followed by 60 mg per day for 1 year) resulting in liver disease (O'Donohue et al. 1993). In that case, the pathological picture is similar to that seen in Wilson disease or the various childhood cirrhosis syndromes associated with excess copper exposure. Experimental animal studies have also demonstrated that ingestion of high amounts of copper in feed can lead to hepatic and renal disease (see section in this chapter on animal studies). A paper by Scheinberg and Sternlieb (1996) is frequently cited as evidence that high concentrations of copper do not cause liver toxicity. That article reported on a study of deaths from cirrhosis among children under

OCR for page 78
Copper in Drinking Water 6 years of age1 exposed to tap water containing copper at 8.5 to 8.8 mg/L in three towns in Massachusetts. The authors reported that no deaths from cirrhosis occurred among those children. However, the crudeness of the end point measured (death), the potentially small number of children actually at risk, and the variability in exposure depending upon whether the child was breast fed or formula fed puts that conclusion into question. The CNS can also be a target of chronic copper toxicity. Generally speaking, reports of neurotoxicity from chronic copper exposure have been limited to humans with Wilson disease. The CNS effects of copper in Wilson individuals are discussed in Chapter 4. Typically, neurological abnormalities have only been reported in animals administered very high doses of copper. Genetic animal models, such as the LEC rat (Mori et al. 1994; Kitaura et al. 1999), and Bedlington terriers with canine copper toxicosis do not have an increased susceptibility to the neurotoxic effects of copper (Owen et al. 1980, Hultgren et al. 1986). Hemolytic anemia due to high concentrations of circulating copper can also occur. Anemia has been seen occasionally in Wilson-disease patients (Scheinberg and Sternlieb 1984; Brewer and Yuzbasiyan-Gurkan 1992) and with copper poisoning in sheep (Gooneratne et al. 1981). In both situations, the anemia is due to a concomitant acute hepatic necrosis (Scheinberg and Sternlieb 1984; Brewer and Yuzbasiyan-Gurkan 1992). That breakdown of the liver cells releases a very large amount of copper into the circulation, damaging red blood cells and causing the acute hemolytic anemia (Scheinberg and Sternlieb 1984; Brewer and Yuzbasiyan-Gurkan 1992). Cessation of menstruation, an increased incidence of gall stones and renal stones, a form of osteoarthritis, and some kidney-function abnormalities can also occur in acute, untreated Wilson patients (Scheinberg and Sternlieb, 1984; Brewer and Yuzbasiyan-Gurkan, 1992). After exposure to exogenous copper in large amounts, acute renal failure can occur and result in permanent renal damage (Chugh et al. 1975; Holtzman et al. 1966). Reproductive and Developmental Toxicity Small amounts of copper from intrauterine devices can prevent embryogenesis by blocking implantation and blastocyst development (Hurley and Keen 1979; Keen 1996; Hanna et al. 1997). In women with untreated Wilson disease, pregnancy is rare and often ends in spontaneous abortion. 1   A total of 64,124 child years based on the average 0–5-year-old population from 1969 to 1991 multiplied by the 23 years in that period.

OCR for page 78
Copper in Drinking Water de Vries, D.J., R.B. Sewell, and P.M. Beart. 1986. Effects of Copper on dopaminergic function in the rat corpus striatum. Exp. Neurol. 91(3):546–558. Dick, A.T., D.W. Dewey, J.M. Gawthorne. 1975. Thiomolybdates. and the copper-molybdenum-sulfur interaction in ruminant nutrition. J. Agr. Sci. 85(3):567–568. Donohue, J. 1997. New ideas after five years of the lead and copper rule: a fresh look at the MCLG for copper. Pp. 265–272 in Advances in Risk Assessment of Copper in the Environment, G.E. Lagos and R. Badilla-Ohlbaum, eds. Santiago, Chile: Catholic University of Chile. Downey, J.S., C.D. Bingle, S. Cottrell, N. Ward, D. Churchman, M. Dobrota, and C.J. Powell. 1998. The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis. Biochem. Blophys. Res. Commun. 244(2): 463–7. DuBois, R.S., O. Rodgerson, G. Martinau, G. Shroter, G. Giles, J. Lilly, C.G. Halgrimson, and T.E. Starzl. 1971. Orthotopic liver transplantation for Wilson's disease. Lancet 13 (March): 505–508. EPA (U.S. Environmental Protection Agency). 1987. Summary Review of the Health Associated with Copper. Health Issue Assessment. EPA/600/8-87/001. Environmental Criteria and Assessment Office, U.S. Environmental Protection Agency, Cincinnati, OH. Epstein, O., R. Spisni, S. Parbhoo, B. Woods, and T. Dormandy. 1982. The effect of oral copper loading and portasystemic shunting on the distribution of copper in the liver, brain, kidney, and cornea of the rat. Am. J. Clin. Nutr. 35(3):551–555. Fairbanks, V.F. 1967. Copper sulfate-induced hemolytic anemia. Inhibition of glucose-6-phosphate dehydrogenase and other possible etiologic mechanisms. Arch. Intern. Med. 120(4):428–32. Ferm, V.H., and D.P. Hanlon. 1974. Toxicity of copper salts in hamster embryonic development. Biol. Reprod. 11(1):97–101. Follesa, P., A. Mallei, S. Floris, M.C. Mostallino, E. Sanna and G. Biggio. 1999. Increased abundance of GABAA receptor subunit mRNAs in the brain of Long-Evans Cinnamon rats, an animal model of Wilson's disease. Brain Res. Mol. Brain Res. 63(2):268–75. Freedman, J.H., M.R. Ciriolo and J. Peisach. 1989. The role of glutathione in copper metabolism and toxicity. J. Biol. Chem. 264(10):5598–605. Fuentealba, I. and S. Haywood. 1988. Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. I. Ultrastructural. changes in the liver. Liver. 8(6):372–380. Ghosh, S. and V.P. Aggarwal. 1962. Accidental poisoning in childhood, with particular reference to kerosene. J. Indian Med. Assoc. 39(Dec.):635–639.

OCR for page 78
Copper in Drinking Water Glass, G.A., and A.A. Stark. 1997. Promotion of glutathione-gamma-glutamyl transpeptidase-dependent lipid peroxidation by copper and ceruloplasmin: the requirement for iron and the effects of antioxidants and antioxidant enzymes. Environ Mol Mutagen 29(1):73–80. Goldstein, S. and G. Czapski. 1986. The role and mechanism of metal ions and their complexes in enhancing damage in biological systems or in protecting these systems from the toxicity of 02–. J. Free Radic. Biol. Med. 2(1):3–11. Gooneratne, S.R., J.M. Howell and J.M. Gawthorne. 1981. An investigation of the effects of intravenous administration of thiomolybdate on copper metabolism in chronic Cu-poisoned sheep. Br. J. Nutr. 46(3): 469–480. Griffin, A.J.B. 1951. Unusual case of copper poisoning. J. R. San. Inst. 71(Jan.):1–8. Halliwell, B. 1989. Free radicals, reactive oxygen species and human disease: a critical evaluation with special reference to atherosclerosis . Br. J. Exp. Pathol. 70(6):737–757. Hanna, L.A., J.M. Peters, L.M. Wiley, M.S. Clegg, C.L. Keen. 1997. Comparative effects of essential and nonessential metals on preimplantation mouse embryo development in vitro. Toxicology 116:123–131. Hansen, M.J. and H.G. Stefan. 1984. Side effects of 58 years of copper sulfate of the Fairmont Lakes, Minnesota. Water Resour. Bull. 20(6):889–900. Harris, Z.L., and J.D. Gitlin. 1996. Genetic and molecular basis for copper toxicity. Am. J. Clin. Nutr. 63(5):836S–841S. Harrison, J.W.E., S.E. Levin, and B. Trabin. 1954. The safety and fate of potassium sodium copper chlorophyllin and other copper compounds. J. Am. Pharm Assoc. 43:722–737. Haywood, S. 1980. The effect of excess dietary copper on the liver and kidney of the male rat. J. Comp. Pathol. 90(2):217–232. Haywood, S. 1985. Copper toxicosis and tolerance in the rat. I. Changes in copper content of the liver and kidney. J. Pathol. 145(2):149–158. Haywood, S. and B. Comerford. 1980. The effect of excess dietary copper on plasma enzyme activity and on the copper content of the blood of the male rat. J. Comp. Pathol. 90(2):233–238. Haywood, S. and M. Loughran. 1985. Copper toxicosis and tolerance in the rat. II. Tolerance—a liver protective adaptation. Liver 5(5):267–275. Haywood, S., M. Loughran and R.M. Batt. 1985a. Copper toxicosis and tolerance in the rat. III. Intracellular localization of copper in the liver and kidney. Exp. Mol. Pathol. 43(2):209–219. Haywood, S., J.J. Trafford and M. Loughran. 1985b. Copper toxicosis and tolerance in the rat: IV. Renal tubular excretion of copper. Br. J. Exp. Pathol. 66(6):699–707.

OCR for page 78
Copper in Drinking Water Haywood, S., I.C. Fuentealba, J. Foster and G. Ross. 1996. Pathobiology of copper-induced injury in Bedlington terriers: ultrastructural and microanalytical studies. Anal. Cell. Pathol. 10(3):229–241. Holmes, N.G., M.E. Herrtage, E.J. Ryder and M.M. Binns. 1998. DNA marker C04107 for copper toxicosis in a population of Bedlington terriers in the United Kingdom. Vet. Rec. 142(14):351–352. Holtzman, N.A., and R.H. Haslam. 1968. Elevation of serum copper following copper sulfate as an emetic. Pediatrics 42(1):189–193. Holtzman, N.A., D.A. Elliott, and R.H. Heller. 1966. Copper intoxication. Report of a case with observations on ceruloplasmin. N. Engl. J. Med. 275(7):347–352. Hopper, S.H., and H.S. Adams. 1958. Copper poisoning from vending machines. Public Health Rep. 73(10):910–914. Horslen, S.P., M.S. Tanner, T.D. Lyon, G.S. Fell, and M.F. Lowry. 1994. Copper associated childhood cirrhosis. Gut 35(10):1497–1500. Howell, J.S. 1958. The effect of copper acetate on p-dimethylaminoazobenzene carcinogenesis in the rat. Br. J. Cancer 12(4):594–608. Hultgren, B.D., J.B. Stevens and R.M. Hardy. 1986. Inherited, chronic, progressive hepatic degeneration in Bedlington terriers with increased liver copper concentrations: clinical and pathologic observations and comparison with other copper-associated liver diseases. Am. J. Vet. Res. 47(2):365–377. Hurley, L.S. and C.L. Keen. 1979. Teratogenic effects of copper. Pp. 33–56 in Copper in the Environment. Part II: Health Effects, J.O. Nriagu, ed. New York: John Wiley & Sons. Iyer, V.N. and W. Szybalski. 1958. Two simple methods for the detection of chemical mutagens. Appl. Microbiol. 6(1):23–29. IPCS (International Programme on Chemical Safety). 1998. Copper. Environmental Health Criteria 200. Geneva: WHO. Jantsch, W., K. Kulig and B.H. Rumack. 1985. Massive copper sulfate ingestion resulting in hepatotoxicity. Clin. Toxicol. 22(6):585–588. Kanematsu, N., M. Hara and T. Kada. 1980. Rec assay and mutagenicity studies on metal compounds. Mutat. Res. 77(2):109–16. Keen, C.L. 1996. Teratogenic effects of essential trace metals: deficiencies and excesses . Pp. 977–1001 in Toxicology of Metals, L.W. Chang, L. Magos, and T. Suzuki, eds. New York: CRC Press. Keen, C.L., B. Lönnerdal and L.S. Hurley. 1982. Teratogenic effects of copper deficiency and excess. Pp.109–121 in Inflammatory Diseases and Copper. J.R.J. Sorenson, ed. Clifton, NJ: Humana Press. Kitaura, K., Y. Chone, N. Satake, A. Akagi, T. Ohnishi, Y. Suzuki and K. Izumi. 1999. Role of copper accumulation in spontaneous renal carcinogenesis in Long-Evans Cinnamon rats. Jpn. J. Cancer Res. 90(4):385–392. Klein W.J., E.N. Metz and A.R. Price. 1972. Acute copper intoxication. A

OCR for page 78
Copper in Drinking Water hazard of hemodialysis. Arch. Intern. Med. 129(4):578–582. Klein, D., J. Lichtmannegger, U. Heinzmann, J. Müller-Höcker, S. Michaelsen, K.H. Summer. 1998. Association of copper to metallothionein in hepatic lysosomes of Long-Evans cinnamon (LEC) rats during the development of hepatitis. Eur. J. Clin. Invest. 28(4):302–310. Kline, R.D., V.W. Hays, and G.L. Cromwell. 1971. Effects of copper, molybdenum and sulfate on performance, hematology and copper stores in pigs and lambs. J. Anim. Sci. 33(4):771–779. Knobeloch, L., M. Ziarnik, J. Howard, B. Theis, D. Farmer, H. Anderson, and M. Proctor. 1994. Gastrointestinal upsets associated with ingestion of copper-contaminated water. Environ. Health Perspect. 102(11): 958–961. Kodama, H. 1996. Genetic disorders of copper metabolism. Pp. 371–386 in Toxicology of Metals, L.W. Chang, L. Magos, and T. Suzuki, eds. Boca Raton, FL: CRC Press. Koizumi, M., J. Fujii, K. Suzuki, T. Inoue, T. Inoue, J.M. Gutteridge and N. Taniguchi. 1998. A marked increase in free copper levels in the plasma and liver of LEC rats: an animal model for Wilson disease and liver cancer. Free Radic. Res. 28(5):441–450. Kok, F.J., C.M. Van Duijn, A. Hofman, G.B. Van der Voet, F.A. De Wolff, C.H. Paays, and H.A. Valkenburg. 1988. Serum copper and zinc and the risk of death from cancer and cardiovascular disease. Am. J. Epidemiol. 128(2):352–359. Lefkowitch, J.H., C.L. Honig, M.E. King, and J.W.C. Hagstrom. 1982. Hepatic copper overload and features of Indian childhood cirrhosis in an American sibship. N. Engl. J. Med. 307(5):271–277. Le Van, J.H., and E.L. Perry. 1961. Copper poisoning on shipboard. Public Health Rep. 76:334. Lecyk, M. 1980. Toxicity of cupric sulfate in mice embryonic development. Zool. Pol. 28:101–105. Li, Y., and M.A. Trush. 1993. DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation. Carcinogenesis 14(7):1303–11. Li, Y., Y. Togashi, S. Sato, T. Emoto, J.H. Kang, N. Takeichi, H. Kobayashi, Y. Kojima, Y. Une and J. Uchino. 1991. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease. J. Clin. Invest. 87(5):1858–1861. Lim, C.T. and K.E. Choo. 1979. Wilson's disease in a 2-year-old child. J. Singapore Paediat. Soc. 11(1&2):99–102. Lindquist, R.R. 1967. Studies on the pathogenesis of hepatolenticular degeneration. I. Acid phosphatase activity in copper-loaded rat livers. Am. J. Pathol. 51(4):471–481. Lindquist, R.R. 1968. Studies on the pathogenesis of hepatolenticular

OCR for page 78
Copper in Drinking Water degeneration. 3. The effect of copper on rat liver lysosomes. Am. J. Pathol. 53(6):903–927. Llewellyn, G.C., E.A. Floyd, G.D. Hoke, L.B. Weekley, and T.D. Kimbrough. 1985. Influence of dietary aflatoxin, zinc, and copper on bone size, organ weight, and body weight in hamsters and rats. Bull. Environ. Contam. Toxicol. 35(2):149–156. Loeb, L.A., E. A. James, A.M. Waltersdorph and S.J. Klebanoff. 1988. Mutagenesis by the autoxidation of iron with isolated DNA. Proc. Natl. Acad. Sci. (USA) 85(11):3918–22. Logue, J.N., M.D. Koontz, and M.A. Hattwick. 1982. A historical prospective mortality study of workers in copper and zinc refineries. J. Occup. Med. 24(5):398–408. Low, B., J.M. Donohue and C.B. Bartley. 1996. A Study on Backflow Prevention Associated with Carbonators. Final Report. NSF International, Ann Arbor, MI. Ludwig, J., G.H. Farr, D.K. Freese, and I. Sternlieb. 1996. Chronic hepatitis and hepatic failure in a 14-year-old girl. Hepatology 22(6):1874–1879. Luo, S.Q., M.C. Plowman, S.M. Hopfer, F.W. Sunderman, Jr. 1993. Embryotoxicity and teratogenicity of Cu2+ and Zn2+ for Xenopus laevis, assayed by the FETAX procedure. Ann. Clin. Lab Sci. 23(2):111–20. Lyle, W.H., J.E. Payton and M. Hui. 1976. Haemodialysis and copper fever. Lancet 1(7973):1324–1325. Ma, Y., D. Zhang, T. Kawabata, T. Kiriu, S. Toyokumi, K. Uchida and S. Okada. 1997. Copper and iron-induced oxidative damage in non-tumor bearing LEC rats. Pathol. Int. 47(4):203–208. Maeda, Y., T. Taira, K. Haraguchi, K. Hirose, A. Kazusaka and S. Fujita. 1997. Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC) rat. Cancer Lett. 119(2):137–141. Maggiore, G., C. De Giacomo, F. Sessa, and G.R. Burgio. 1987. Idiopathic hepatic copper toxicosis in a child. J. Pediatr. Gastroenterol. Nutr. 6(6):980–983. Makale, M.T., and G.L. King. 1992. Surgical and pharmacological dissociation of cardiovascular and emetic responses to intragastric CuSO4. Am. J. Physiol. 263(2 Pt 2):R284–R291. Malins, D.C., N.L. Polissar and S.J. Gunselman. 1996. Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation. Proc. Natl. Acad. Sci. (USA) 93(24):14047–52. Manzler, A.D. and A.W. Schreiner. 1970. Copper-induced acute hemolytic anemia. A new complication of hemodialysis. Arch. Intern. Med. 73(3):409–412. Marois, M., and M. Bovet. 1972. Effect of copper ions on pregnancy in

OCR for page 78
Copper in Drinking Water rats and rabbits [in French]. CR Soc. Biol. 166(10):1237–1240. Marzin, D.R. and H.V. Phi. 1985. Study of the mutagenicity of metal derivatives with Salmonella typhimurium TA102. Mutat. Res. 155(1–2): 49–51. Mason, J. 1990. The biochemical pathogenesis of molybdenum-induced copper deficiency in ruminants: towards the final chapter. Irish Vet. J. 43(1):18–21. Massie, H.R. and V.R. Aiello. 1984. Excessive intake of copper: influence on longevity and cadmium accumulation in mice. Mech. Ageing Dev. 26(2–3):195–203. Matsui, S. 1980. Evaluation of a Bacillus subtilis rec-assay for detection of mutagens which may occur in water environments. Water Res. 14(11):1613–1619. Matsumoto, A., R. Hanayama, M. Nakamura, K. Suzuki, J. Fujii, H. Tatsumi, and N. Taniguchi. 1998. A high expression of heme oxygenase-1 in the liver of LEC rats at the stage of hepatoma: the possible implication of induction in uninvolved tissue. Free Radic. Res. 28(4): 383–391. Matter, B.J., J. Pederson, G. Psimenos and R.D. Lindeman. 1969. Lethal copper intoxication in hemodialysis. Trans. Am. Soc. Artif. Intern. Organs 15:309–315. McMullen, W. 1971. Copper contamination of soft drinks from bottle pourers. Health Bull. (Edinb.) 29(2):94–96. McNatt, E.N., W.R. Campbell Jr., and B.C. Callahan. 1971. Effects of dietary copper loading on livers of rats. I. Changes in subcellular acid phosphatases and detection of an additional acid p-nitrophenylphosphatase in the cellular supernatant during copper loading. Am. J. Pathol. 64(1):123–144. Miller, D.M., G.R. Buettner and S.D. Aust. 1990. Transition metals as catalysts of ''autoxidation" reactions. Free Radic. Biol. Med. 8(1):95–108. Mittal, S.R. 1972. Oxyhaemoglobinuria following copper sulphate poisoning: a case report and a review of the literature. Forensic Sci. 1(2):245–248. Montaser, A., C. Tetreault, and M. Linder. 1992. Comparison of copper binding components in dog serum with those in other species. Proc. Soc. Exp. Biol. Med. 200(3):321–329. Moore, G.S., and E.J. Calabrese. 1980. G6PD-deficiency: A potential highrisk group to copper and chlorite ingestion. J. Environ. Pathol. Toxicol. 4(2–3):271–279. Mori, M., A. Hattori, M. Sawaki, N. Tsuzuki, N. Sawada, M. Oyamada, N. Sugawara, and K. Enomoto. 1994. The LEC rat: a model for human hepatitis, liver cancer, and much more. Am. J. Pathol. 144(1):200–204.

OCR for page 78
Copper in Drinking Water Moriya, M., T. Ohta, K. Watanabe, T. Miyazawa, K. Kato, and Y. Shirasu. 1983. Further mutagenicity studies on pesticides in bacterial reversion assay systems. Mutat. Res. 116(3–4):185–216. Mudassar, S., K.I. Andrabi, M. Khullar, N.K. Ganguly and B.N. Walia. 1992. Effect of exogenous copper on lipid peroxidation in rat hepatocytes. Possible involvement of protein kinase C. J. Pharm. Pharmacol. 44(7):609–611. Müller, T., H. Feichtinger, H. Berger and W. Müller. 1996. Endemic tyrolean infantile cirrhosis: an exogenetic disorder. Lancet 347(9005):877–880. Müller, T.H., W. Müller and H. Feichtinger. 1998. Idiopathic copper toxicosis. Am. J. Clin. Nutr. 67(5 Suppl.): 1082S–1086S. Müller-Höcker, J., U. Meyer, B. Wiebecke, G. Hübner, R. Eife, M. Kellner, P. Schramel. 1988. Copper storage disease of the liver and chronic dietary copper intoxication in two further German infants mimicking Indian childhood cirrhosis. Pathol. Res. Pract. 183(1):39–45. Müller-Höcker, J., M. Weiss, U. Meyer, P. Schramel, B. Wiebecke, B.H. Belohradsky, G. Habner. 1987. Fatal copper storage disease of the liver in a German infant resembling Indian childhood cirrhosis. Virchows. Arch. A. Pathol. Anat. Histopathol. 411(4):379–385. Muramatsu Y., T. Yamada, D.H. Moralejo, Y. Suzuki, and K. Matsumoto. 1998. Fetal copper uptake and a homolog (Atp7b) of the Wilson's disease gene in rats. Res. Commun. Mol. Pathol. Pharmacol. 101(3):225–231. Murthy, R.C., S. Lal, D.K. Saxena, G.S. Shukla, M.M. Ali, and S.V. Chandra. 1981. Effect of manganese and copper interaction on behavior and blogenic amines in rats fed a 10% casein diet. Chem. Biol. Interact. 37(3):299–308. Myers, B.M., F.G. Prendergast, R. Holman, S.M. Kuntz, and N.F. Larusso. 1993. Alterations in hepatocyte lysosomes in experimental hepatic copper overload in rats. Gastroenterology 105(6):1814–1823. Nagano, K., K. Nakamura, K.I. Urakami, K. Umeyama, H. Uchiyama, K. Koiwai, S. Hattori, T. Yamamoto, I. Matsuda and F. Endo. 1998. Intracellular distribution of the Wilson's disease gene product (ATPase7B) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson's disease. Hepatology 27(3):799–807. Nakamura, K., F. Endo, T. Ueno, H. Awata, A. Tanoue and I. Matsuda. 1995. Excess copper and ceruloplasmin biosynthesis in long-term cultured hepatocytes from Long-Evans Cinnamon (LEC) rats, a model of Wilson disease. J. Biol. Chem. 270(13):7656–7660. Nicholas, P.O. 1968. Food poisoning due to copper in the morning tea Lancet 2(7558):40–42. Nieminen, A.L., and J.J. Lemasters. 1996. Hepatic injury by metal accu

OCR for page 78
Copper in Drinking Water mulation. Pp. 887–899 in Toxicology of Metals, L.W. Chang, ed. Boca Raton, FL.: CRC Press. Nishioka, H. 1975. Mutagenic activities of metal compounds in bacteria. Mutat. Res. 31(3):185–9. NRC (National Research Council). 1977. Copper. Washington, D.C.: National Academy of Sciences. NTP (National Toxicology Program). 1993. NTP Technical Report on Toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice. NTIS PB94-120870. O'Donohue, J., M.A. Reid, A. Varghese, B. Portmann, R. Williams. 1993. Micronodular cirrhosis and acute liver failure due to chronic copper self-intoxication. Eur. J. Gastroenterol. Hepatol. 5:561–562. Ogra, Y. and K.T. Suzuki. 1998. Targeting of tetrathiomolybdate on the copper accumulating in the liver of LEC rats. J. Inorg. Biochem. 70(1): 49–55. Olivier, P. and D. Marzin. 1987. Study of the genotoxic potential of 48 inorganic derivatives with the SOS chromotest. Mutat. Res. 189(3):263–9. Overvad, K., D.Y. Wang, J. Olsen, D.S. Allen, E.B. Thorling, R.D. Bulbrook, and J.L. Hayward. 1993. Copper in human mammary carcinogenesis: a case-cohort study. Am. J. Epidemiol. 137(4):409–414. Owen, C.A. Jr., E.J. Bowie, J.T. McCall, and P.E. Zollman. 1980. Hemostasis in the copper-laden Bedlington terrier: a possible model of Wilson's disease. Haemostasis 9(3):160–166. Percival T. 1784. A history of the fatal effects of pickles impregnated with copper, together with observations on that mineral poison. Med. Trans. R. Coll. Phys. (London) 3:80–95. Pizarro, F., M. Olivares, R. Uauy, P. Contreras, A. Rebelo, and V. Gidi. 1999. Acute gastrointestinal effects of graded levels of copper in drinking water. Environ. Health Perspect. 107(2):117–121. Prasad, R., G. Kaur, R. Mond, B.N. Walia. 1998. Identification of a novel copper-binding protein from the liver of Indian childhood cirrhosis: purification and physicochemical characterization. Pediatr. Res. 44(5):673–681. Prasad, M.P., T.P. Krishna, S. Pasricha, K. Krishnaswamy, and M.A. Quereshi. 1992. Esophageal cancer and diet—a case-control study. Nutr. Cancer 18(1):85–93. Rana, S.V.S. and A. Kumar. 1980. Biological haematological and histological observations in copper poisoned rats. Ind. Health. 18:9–17. Rauch, H. 1983. Toxic milk, a new mutation affecting cooper metabolism in the mouse. J. Hered. 74(3):141–4. Roberts, R.H. 1956. Hemolytic anemia associated with copper sulfate poisoning. Mississipi Doctor 33(March):292–294. Roberts, L.F., B. Ashby, E.G. Hallock and M. McGeehin. 1996. Ability of

OCR for page 78
Copper in Drinking Water Household Consumers to Tolerate Elevated Copper Levels in Drinking Water: Delaware, 1996. Draft. National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA. Ross, A.I. 1955. Vomiting and diarrhea due to copper in stewed apples. Lancet (July 9):87–88. Rui, M. and K.T. Suzuki. 1997. Copper in plasma reflects its status and subsequent toxicity in the liver of LEC rats. Res. Commun. Mol. Pathol. Pharmacol. 98(3):335–346. Runner, M. N., and J. R. Miller. 1956. Congenital deformity in the mouse as a consequence of fasting. Anat. Rec. 124:437–438. Saito, T., T. Nagao, M. Okabe, K. Saito. 1996. Neurochemical and histochemical evidence for an abnormal catecholamine metabolism in the cerebral cortex of the Long-Evans Cinnamon rat before excessive copper accumulation in the brain. Neurosci. Lett. 216(3):195–198. Saito, R., Y. Suehiro, H. Ariumi, K. Migita, N. Hori, T. Hashiguchi, M. Sakai, M. Saeki, Y. Takano, and H. Kamiya. 1998. Anti-emetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets. Neurosci. Lett. 254(3):169–172. Salmon, M.P., and T. Wright. 1971. Chronic copper poisoning presenting as pink disease. Arch. Dis. Child. 46(245):108–110. Sanghvi, L.M., R. Sharma, S.N. Misra and K.C. Samuel. 1957. Sulfhemoglobinemia and acute renal failure after copper sulfate poisoning. Report of two fatal cases. Arch. Pathol. 63:172–175. Scheinberg, I.H. and I. Sternlieb. 1984. Wilson's disease. Major Problems in Internal Medicine. Vol. 23. Philadelphia: W.B. Saunders. Scheinberg, I.H., and I. Sternlieb. 1996. Wilson disease and idiopathic copper toxicosis. Am. J. Clin. Nutr. 63(5):842S–845S. Semple, A.B., W.H. Parry and D.E. Phillips. 1960. Acute copper poisoning. An outbreak traced to contaminated water from a corroded geyser. Lancet 2:700–701. Shanaman, J.E. 1972. Report of One Year Chronic Oral Toxicity of Copper Gluconate W10219A in Beagle Dogs. Research Rep. No. 955-0353. Morris Plains, NJ: Warner Lambert Research Institute. Shanaman, J.E., F.X. Wazeter, E.I. Goldenthal. 1972. One-Year Chronic Oral Toxicity of Copper Gluconate W/02/09A in Beagle Dogs. Research Rep. No. 955-0353. Morris Plains, NJ: Warner Lambert Research Institute. Singh, M.M. and G. Singh. 1968. Biochemical changes in blood in cases of acute copper sulphate poisoning. J. Indian Med. Assoc. 50(12):449–554. Sokol, R.J., M.W. Devereaux, M.G. Traber and R.H. Shikes. 1989. Copper toxicity and lipid peroxidation in isolated rat hepatocytes: effect of vitamin E. Pediatr. Res. 25(1):55–62. Spitalny, K.C., J. Brondum, R.L. Vogt, H.E. Sargent, and S. Kappel. 1984.

OCR for page 78
Copper in Drinking Water Drinking water induced copper intoxication in a Vermont family. Pediatrics 74(6):1103–1106. Stein, R.S., D. Jenkins, and M.E. Korns. 1976. Death after use of cupric sulfate as an emetic [letter]. JAMA 235(8):801. Steinebach, O.M. and H.T. Wolterbeek. 1994. Role of cytosolic copper, metallothionein and glutathione in copper toxicity in rat hepatoma tissue culture cells. Toxicology 92(1–3):75–90. Stenhammer, L. 1979. Copper intoxication: a differential diagnosis of diarrhea in children [in Swedish]. Lakartidningen 76(30–31):2618–2620. Stoner, G.D., M.B. Shimkin, M.C. Troxell, T.L. Thompson, and L.S. Terry. 1976. Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice. Cancer Res. 36(5):1744–1747. Suttle, N.F. and C.F. Mills. 1966. Studies of the toxicity of copper to pigs. I. Effects of oral supplements of zinc and iron salts on the development of copper toxicosis. Br. J. Nutr. 20(2):135–148. Suzuki, K.T. 1995. Disordered copper metabolism in LEC rats, an animal model of Wilson disease: roles of metallothionein. Res. Commun. Mol. Pathol. Pharmacol. 89(2):221–240. Suzuki, K.T., M. Rui, J. Ueda and T. Ozawa. 1996. Production of hydroxyl radicals by copper-containing metallothionein: roles as prooxidant. Toxicol. Appl. Pharmacol. 141(1):231–237. Tachibana, K. 1952. Pathological transition and functional vicissitude of liver during formation of cirrhosis by copper. Nagoya J. Med Sci. 15:108–114. Tanner, M.S. 1998. Role of copper in Indian childhood cirrhosis. Am. J. Clin. Nutr. 67(5 Suppl.):1074S–1081S. Tanner, M.S., and A.R. Mattocks. 1987. Hypothesis: plant and fungal blocides, copper and Indian childhood liver disease. Ann. Trop. Pediatr. 7(4):264–269. Tanner, M.S., A.H. Kantarjian, S.A. Bhave and A.N. Pandit. 1983. Early introduction of copper-contaminated animal milk feeds as a possible cause of Indian childhood cirrhosis. Lancet 2(8357):992–995. Terada, K., N. Aiba, X.L. Yang, M. Iida, M. Nakai, N. Miura and T. Sugiyama. 1999. Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B. FEBS Lett. 448(1):53–56. Terada, K., M.L. Schilsky, N. Miura and T. Sugiyama. 1998. ATP7B (WND) protein . Int. J. Blochem. Cell Biol. 30(10):1063–1067. Tkeshelashvili, L.K., T. McBride, K. Spence and L.A. Loeb. 1991. Mutation spectrum of copper-induced DNA damage. J. Biol. Chem. 266(10): 6401–6406. van de Sluis, B.J., M. Breen, M. Nanji, M. van Wolferen, P. de Jong, M.M. Binns, P.L. Pearson, J. Kuipers, J. Rothuizen, D.W. Cox, C. Wijmenga,

OCR for page 78
Copper in Drinking Water and B.A. van Oost. 1999. Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13–p16. Hum. Mol. Genet. 8(3):501–507. von Rosen, G. 1964. Mutations induced by action of metal ions in Pisum II. Hereditas 51(1):89–134. Vulpe, C.D. and S. Packman. 1995. Cellular copper transport. Annu. Rev. Nutr. 15:293–322. Wahal, P.K., V.P. Mittal, and O.P. Bansal. 1965. Renal complications in acute copper sulphate poisoning. Indian Pract. 18:807–812. Walker-Smith, J. and J. Blomfield. 1973. Wilson's disease or chronic copper poisoning? Arch. Dis. Child. 48(6):476–479. Walsh, F.M., F.J. Crosson, M. Bayley, J. McReynolds, and B.J. Pearson. 1977. Acute copper intoxication. Pathophysiology and therapy, with a case report. Am. J. Dis. Child. 131(2):149–151. Wang, S.C. and H.I. Borison. 1951. Copper sulphate emesis: study of afferent pathways from the gastrointestinal tract. Am. J. Physiol. 164:520–526. Wapnir, R.A. 1998. Copper absorption and bioavailability. Am. J. Clin. Nutr. 67(5 Suppl.):1054S–1060S. Wong, P.K. 1988. Mutagenicity of heavy metals. Bull. Environ. Contam. Toxicol. 40(4):597–603. Wu, J., J.R. Forbes, H.S. Chen, and D.W. Cox. 1994. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene . Nat. Genet. 7(4):541–545. Wyllie, J. 1957. Copper poisoning at a cocktail party. Am. J. Publ. Health 47:617. Yuzbasiyan-Gurkan, V., B.S. Halloran, Y. Cao, P. Ferguson, J. Li, P.J. Venta, G.J. Brewer. 1997. Linkage of a microsatellite marker to the canine copper toxicosis locus in Bedlington terriers. Am. J. Vet. Res. 58(1):23–27.