doi:10.1016/S0048-9697(02)00399-6 
Copyright © 2002 Elsevier Science B.V. All rights reserved.
Epidemiological investigation on chronic copper toxicity to children exposed via the public drinking water supply
Björn P. Zietz
, 
, a, Hermann H. Dieterb, Max Lakomekc, Heide Schneidera, Barabara Keßler-Gaedtkea and Hartmut Dunkelberga
a Medical Institute of General Hygiene and Environmental Health, University of Göttingen, Windausweg 2, D-37073, Göttingen, Germany
b Department for Water-, Soil and Air Hygiene, Federal Environmental Agency, Corrensplatz 1, D-14195, Berlin, Germany
c Department of Pediatrics, University of Göttingen, Robert-Koch-Straße 40, D-37075, Göttingen, Germany
Received 2 July 2002;
accepted 11 September 2002. ;
Available online 2 December 2002.
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Abstract
Copper in drinking water has been associated with Non-Indian Childhood Cirrhosis (NICC), a form of early childhood liver cirrhosis. This epidemiological study examines the exposition of infants to increased copper concentrations through drinking water from public water supplies in Berlin, Germany, and if this dietary copper intake can cause liver damage in early childhood. In total, water samples from 2944 households with infants were tested for copper. Mean copper concentrations in the two different types of collected composite samples were 0.44 and 0.56 mg/l, respectively. Families having a copper concentration at or above 0.8 mg/l in one or both of the composite samples (29.9% of all sampled households) and a defined minimum ingestion of tap water of their infant were recommended to undergo a paediatric examination. Nearly every of the 541 recommended infants were examined by a local paediatrician and of these 183 received a blood serum analysis, too. None of the infants had clear signs of a liver disease although a few serum parameters lay outside the accompanying reference range and abdominal ultrasound imaging gave slightly unusual results in five cases. Additionally, no signs of a negative health effect could be found in the statistical analysis of the serum parameters GOT, GPT, GGT, total bilirubin, serum copper, or ceruloplasmin in relation to estimated daily and total copper intakes of the infants from tap water. No dose relation of serum parameters and estimated copper intakes could be established. From the results of the study, no confirmed indication of a liver malfunction in infants whose food had been prepared using tap water with an elevated copper concentration could be found and, therefore, no indication of a hazard due to copper pipes connected to public water supplies could be detected.
Author Keywords: Copper; Heavy metals; Non-Indian Childhood Cirrhosis, NICC; Public water supply; Tap water
Fig. 1. Mean copper concentrations and stated age of installation in composite sample type 1 and 2 (excluding samples collected in relation to screening samples).
Fig. 2. Frequencies of all measured infant values of serum GOT, GPT and GGT grouped in classes.
Fig. 3. (a) Serum GOT and estimated total copper intake through tap water (calculated with copper concentrations from composite sample type 1) including linear trend line (Excel®). Spearman rank correlation −0.090 with P=0,228 (2-tailed). (b) Serum GOT and estimated daily copper intake through tap water (calculated with copper concentrations from composite sample type 1) including linear trend line. Spearman rank correlation −0.060 with P=0.422 (2-tailed). (c) Serum copper and estimated total copper intake through tap water (calculated with copper concentrations from composite sample type 1) including linear trend line. Spearman rank correlation −0.071 with P=0.357 (2-tailed). (d) Total bilirubin and estimated total copper intake through tap water (calculated with copper concentrations from composite sample type 1) including linear trend line. Spearman rank correlation 0.101 with P=0.201 (2-tailed).
Table 1. Statistic overview of composite samples type 1 and 2 taken independently of screening samples
Table 2. Chemical and physical parameters of selected households located in different suburbs of Berlina
Table 3. Results of blood serum analyses of infants exposed to elevated copper concentrations having outliers in their serum parameters (serum copper, GOT, GPT, GGT) or unusual ultrasound images of the liver or spleen or serum analyses that were repeated
Used reference values: GOT 2nd–12th month <28 mU/ml, >12 months <23 mU/ml (
Witt and Trendelenburg, 1982); GPT 2nd–12th month <31 mU/ml, >12 months <25 mU/ml (
Witt and Trendelenburg, 1982); GGT 2nd–12th month up to 100 mU/ml, >12 months <21 mU/ml (
Witt and Trendelenburg, 1982); total bilirubin 2 months and older: up to 1 mg/dl (
Witt and Trendelenburg, 1982); Ceruloplasmin 15–60 mg/dl (
Thomas, 1984); IgM 7th–12th month 0.36–1.04 g/l, 2 years 0.72–1.60 g/l (
Uffelmann et al., 1970); IgG 7th–12th month 3.5–11.8 g/l, 2 years 5.2–10.8 g/l (
Uffelmann et al., 1970); IgA 7th–12th month and 2 years 0.36–1.65 g/l (
Uffelmann et al., 1970); CRP up to 1 mg/dl (
Sabel and Wadsworth, 1979). Serum copper: 6th–12th month mean 136–161 μg/dl, standard deviation 24–32 μg/dl (
Kirsten et al., 1985). n.t.=Not tested; B2437a and B2437b are twins.
aBlood serum tested in foreign laboratory.
Table 4. Means of serum parameters in three different exposition groups (total copper intake with tap water) calculated for all serum parameters (n=183), serum parameters measured in the Göttingen laboratory (n=124) and all serum parameters excluding outliers (n=175)
Remarks: total copper intake estimated with copper concentrations in composite samples type 1; in the third part of the table records of infants with outliers of serum copper, GOT, GPT, GGT, ceruloplasmin were excluded completely (there were no outliers of total bilirubin); calculation method of free copper is described in the text.
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