| | | | |
Children's Health
|
Renal and Neurologic Effects of Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple Interactions at Environmental Exposure Levels Claire de Burbure,1 Jean-Pierre Buchet,1 Ariane Leroyer,2 Catherine
Nisse,2 Jean-Marie Haguenoer,2 Antonio Mutti,3 Zdenek
Smerhovsky´,4 Miroslav Cikrt,4 Malgorzata Trzcinka-Ochocka,5 Grazyna
Razniewska,5 Marek Jakubowski,5 and Alfred Bernard1 1Unit of Industrial Toxicology and Occupational Medicine, Faculty
of Medicine, Catholic University of Louvain, Belgium; 2Centre de
recherches en santé-travail-ergonomie-Laboratoire Universitaire de Médecine
du Travail, Université Lille 2, Lille, France; 3Laboratorio
di Tossicologia Industriale, Universita degli Studi di Parma, Parma, Italy; 4National
Institute of Public Health, Prague, Czech Republic; 5Nofer Institute
of Occupational Medicine, Lodz, Poland Abstract Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children’s health is little known. We studied their effects on two main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and β2-microglobulin were negatively correlated with blood lead levels (PbB) , suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> 55 µg/L ; mean, 78.4 µg/L) . The urinary excretion of retinol-binding protein, Clara cell protein, and N-acetyl-β-d-glucosaminidase was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children’s renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals. Key words: arsenic, biomarkers, cadmium, dopaminergic, heavy metals, interactions, lead, mercury, renal. Environ Health Perspect 114:584-590 (2006) . doi:10.1289/ehp.8202 available via http://dx.doi.org/ [Online 20 October 2005]
Address correspondence to A. Bernard, Unit of Industrial Toxicology and Occupational Medicine, Université Catholique de Louvain, Clos Chapelle-aux-Champs 30, bte 3054, B-1200 Brussels, Belgium. Telephone: 32-2-7643220. Fax: 32-2-7643228. E-mail: bernard@toxi.ucl.ac.be This study was supported by the Fourth and Fifth Research, Technological Development and Demonstration programs of the European Commission and by the French Association for Metals and Health (AMSE) . A.B. is Research Director of the National Fund for Scientific Research, Belgium. The authors declare they have no competing financial interests. Received 13 April 2005 ; accepted 19 October 2005. |
|
|
|
|
|
[References Listed in PubMed] References
Alvarez Leite EM, Leroyer A, Nisse
C, Haguenoer JM, de Burbure CY, Buchet
JP, et al. 2002. Urinary homovanillic
acid and serum prolactin levels in
children with low environmental exposure
to lead. Biomarkers 7:49-57.
Bernard A, Hermans C. 1997. Biomonitoring
of early effects on the kidney or the
lung. Sci Total Environ 199:205-211.
Bernard AM, Vyskocil A, Lauwerys
RR. 1981. Determination of beta 2-microglobulin
in human urine and serum by latex immunoassay.
Clin Chem 27:832-837.
Bernard AM, Vyskocil A, Roels H,
Kriz J, Kodl M, Lauwerys R. 1995. Renal
effects in children living in the vicinity
of a lead smelter. Environ Res 68:91-95.
Bland JM, Altman DG. 1986. Statistical
methods for assessing agreement between
two methods of clinical measurement.
Lancet 1(8476):307-310.
Buchet JP, Heilier JF, Bernard A,
Lison D, Jin T, Wu X, et al. 2003.
Urinary protein excretion in humans
exposed to arsenic and cadmium. Int
Arch Occup Environ Health 76:111-120.
Camerino D, Buratti M, Rubino FM,
Somaruga C, Belluigi V, Bordiga A,
et al. 2002. [Evaluation of the neurotoxic
and nephrotoxic effects following long-term
exposure to metallic mercury in employees
at a chlorine/sodium-hydroxide plant;
in Italian]. Med Lav 93:238-250.
Carta P, Flore C, Alinovi R, Ibba
A, Tocco MG, Aru G, et al. 2003. Sub-clinical
neurobehavioral abnormalities associated
with low level of mercury exposure
through fish consumption. Neurotoxicology
24:617-623.
Courtois E, Marques M, Barrientos
A, Casado S, Lopez-Farre A. 2003. Lead-induced
downregulation of soluble guanylate
cyclase in isolated rat aortic segments
mediated by reactive oxygen species
and cyclooxygenase-2. J Am Soc Nephrol
14:1464-1470.
Davidson PW, Myers GJ, Weiss B. 2004.
Mercury exposure and child development
outcomes. Pediatrics 113: 1023-1029.
de Burbure C, Buchet JP, Bernard
A, Leroyer A, Nisse C, Haguenoer JM,
et al. 2003. Biomarkers of renal effects
in children and adults with low environmental
exposure to heavy metals. J Toxicol
Environ Health A 66: 783-799.
Delgado JM, Dufour L, Grimaldo JI,
Carrizales L, Rodriguez VM, Jimenez-Capdeville
ME. 2000. Effects of arsenite on central
monoamines and plasmatic levels of
adrenocorticotropic hormone (ACTH)
in mice. Toxicol Lett 117: 61-67.
Donadio C, Lucchesi A, Ardini M,
Giordani R. 2001. Cystatin C, beta
2-microglobulin, and retinol-binding
protein as indicators of glomerular
filtration rate: comparison with plasma
creatinine. J Pharm Biomed Anal 24:835-842.
Faro LR, Duran R, Do Nascimento JL,
Perez-Vences D, Alfonso M. 2003. Effects
of successive intrastriatal methylmercury
administrations on dopaminergic system.
Ecotoxicol Environ Saf 55:173-177.
Fels LM, Wunsch M, Baranowski J,
Norska-Borowka I, Price RG, Taylor
SA, et al. 1998. Adverse effects of
chronic low level lead exposure on
kidney function--a risk group study
in children. Nephrol Dial Transplant
13:2248-2256.
Fowler BA. 1996. The nephropathology
of metals. In: Toxicology of Metals
(Chang LW, ed). Boca Raton, FL: CRC
Lewis, 721-729.
Fowler BA. 1998. Roles of lead-binding
proteins in mediating lead bioavailability.
Environ Health Perspect 106(suppl 6):1585-1587.
Friedman AN. High-protein diets:
potential effects on the kidney in
renal health and disease. 2004. Am
J Kidney Dis 44:950-962.
Govoni S, Battaini F, Fernicola C,
Castelletti L, Trabucchi M. 1987. Plasma
prolactin concentrations in lead exposed
workers. J Environ Pathol Toxicol Oncol
7:13-15.
Hotz P, Buchet JP, Bernard A, Lison
D, Lauwerys R. 1999. Renal effects
of low-level environmental cadmium
exposure: 5-year follow-up of a subcohort
from the Cadmibel study. Lancet 354:1508-1513.
Jakubowski M, Trzcinka-Ochocka M,
Razniewska G, Christensen JM, Starek
A. 1996. Blood lead in the general
population in Poland. Int Arch Occup
Environ Health 68: 193-198.
Khalil-Manesh F, Gonick HC, Cohen
AH, Alinovi R, Bergamaschi E, Mutti
A, et al. 1992. Experimental model
of lead nephropathy. I. Continuous
high-dose lead administration. Kidney
Int 41:1192-1203.
Lafuente A, Cano P, Esquifino A.
2003a. Are cadmium effects on plasma
gonadotropins, prolactin, ACTH, GH
and TSH levels, dose-dependent? Biometals
16:243-250.
Lafuente A, Gonzalez-Carracedo A,
Romero A, Esquifino AI. 2003b. Effect
of cadmium on 24-h variations in hypothalamic
dopamine and serotonin metabolism in
adult male rats. Exp Brain Res 149:200-206.
Leroyer A, Hemon D, Nisse C, Auque
G, Mazzuca M, Haguenoer JM. 2001. Determinants
of cadmium burden levels in a population
of children living in the vicinity
of nonferrous smelters. Environ Res
87:147-159.
Leroyer A, Nisse C, Hemon D, Gruchociak
A, Salomez JL, Haguenoer JM. 2000.
Environmental lead exposure in a population
of children in northern France: factors
affecting lead burden. Am J Ind Med
38:281-289.
Lidsky TL, Schneider JS. 2003. Lead
neurotoxicity in children: basic mechanisms
and clinical correlates. Brain 126:5-19.
Lucchini R, Albini E, Cortesi I,
Placidi D, Bergamaschi E, Traversa
F, et al. 2000. Assessment of neurobehavioral
performance as a function of current
and cumulative occupational lead exposure.
Neurotoxicology 21: 805-811.
Pohl HR, Roney N, Wilbur S, Hansen
H, De Rosa CT. 2003. Six interaction
profiles for simple mixtures. Chemosphere
53:183-197.
Price RG, Taylor SA, Chivers I, Arce-Tomas
M, Crutcher E, Franchini I, et al.
1996. Development and validation of
new screening tests for nephrotoxic
effects. Hum Exp Toxicol 15(suppl 1):S10-S19.
Risch L, Blumberg A, Huber A. 1999.
Rapid and accurate assessment of glomerular
filtration rate in patients with renal
transplants using serum cystatin C.
Nephrol Dial Transplant 14:1991-1996.
Rodriguez VM, Dufour L, Carrizales
L, Diaz-Barriga F, Jimenez-Capdeville
ME. 1998. Effects of oral exposure
to mining waste on in vivo dopamine
release from rat striatum. Environ
Health Perspect 106:487-491.
Roels H, Lauwerys R, Konings J, Buchet
JP, Bernard A, Green S, et al. 1994.
Renal function and hyperfiltration
capacity in lead smelter workers with
high bone lead. Occup Environ Med 51:505-512.
Roels HA, Van Assche FJ, Oversteyns
M, De Groof M, Lauwerys RR, Lison D.
1997. Reversibility of microproteinuria
in cadmium workers with incipient tubular
dysfunction after reduction of exposure.
Am J Ind Med 31: 645-652.
Staessen JA, Nawrot T, Hond ED, Thijs
L, Fagard R, Hoppenbrouwers K, et al.
2001. Renal function, cytogenetic measurements,
and sexual development in adolescents
in relation to environmental pollutants:
a feasibility study of biomarkers.
Lancet 357:1660-1669.
Verberk MM, Willems TE, Verplanke
AJ, De Wolff FA. 1996. Environmental
lead and renal effects in children.
Arch Environ Health 51:83-87.
Weaver VM, Lee BK, Ahn KD, Lee GS,
Todd AC, Stewart WF, et al. 2003a.
Associations of lead biomarkers with
renal function in Korean lead workers.
Occup Environ Med 60:551-562.
Weaver VM, Schwartz BS, Ahn KD, Stewart
WF, Kelsey KT, Todd AC, et al. 2003b.
Associations of renal function with
polymorphisms in the delta-aminolevulinic
acid dehydratase, vitamin D receptor,
and nitric oxide synthase genes in
Korean lead workers. Environ Health
Perspect 111: 1613-1619.
Last Updated: March 16, 2006 |
|
|
|
| |