OBJECTIVES: Concern on human renal toxicity and carcinogenicity of trichloroethylene is based on findings of increased incidences of renal cell cancers in persons with long-lasting and high occupational exposures to this solvent. The full tumour development is likely to require promotional stimuli, by repetitive episodes of high peak exposures to trichloroethylene, leading to nephrotoxicity. This process is visualised by the excretion of tubular marker proteins in the urine of exposed persons. For this purpose, surveillance of alpha1-microglobulin excretion is being suggested by the Deutsche Forschungsgemeinschaft. METHODS: The present study assessed the applicability of alpha1-microglobulin as a biomarker of proximal tubule damage in the prevention of nephrotoxicity by trichloroethylene exposures. For this purpose, alpha1-microglobulin excretions were assessed in trichloroethylene-exposed and non-exposed subgroups of both cases (diseased with renal cancer) and controls (not diseased with renal cancer) of a recent case-control study. RESULTS: The median of alpha1-microglobulin excretions in non-exposed persons was below the detection limit, but it was clearly elevated in exposed persons. The Wilcoxon rank sum test showed a significant difference ( P=0.0090). Consistent with the underlying concept, renal cell cancer cases who had been exposed to trichloroethylene had higher alpha1-microglobulin excretions than non-exposed cases ( P=0.0005) and also had higher alpha1-microglobulin excretions than exposed controls ( P=0.0004). Of 20 trichloroethylene-exposed renal cell cancer cases only three (15%) displayed a normal alpha1-microglobulin excretion of <5 mg/l. By contrast, 41 (52%) out of 79 non-exposed renal cancer cases showed normal excretions of the biomarker. CONCLUSION: The present data are in agreement with the concept of pathogenesis of renal cell cancers developing under high (suggested: >500 ppm peak exposures) and long-term (several years) exposure to trichloroethylene. They also visualise the potential value of alpha1-microglobulin excretion as a routine biomarker of renal toxicity that may be used in the medical surveillance of trichloroethylene-exposed persons.
OBJECTIVES: Concern on humanrenal toxicity and carcinogenicity of trichloroethylene is based on findings of increased incidences of renal cell cancers in persons with long-lasting and high occupational exposures to this solvent. The full tumour development is likely to require promotional stimuli, by repetitive episodes of high peak exposures to trichloroethylene, leading to nephrotoxicity. This process is visualised by the excretion of tubular marker proteins in the urine of exposed persons. For this purpose, surveillance of alpha1-microglobulin excretion is being suggested by the Deutsche Forschungsgemeinschaft. METHODS: The present study assessed the applicability of alpha1-microglobulin as a biomarker of proximal tubule damage in the prevention of nephrotoxicity by trichloroethylene exposures. For this purpose, alpha1-microglobulin excretions were assessed in trichloroethylene-exposed and non-exposed subgroups of both cases (diseased with renal cancer) and controls (not diseased with renal cancer) of a recent case-control study. RESULTS: The median of alpha1-microglobulin excretions in non-exposed persons was below the detection limit, but it was clearly elevated in exposed persons. The Wilcoxon rank sum test showed a significant difference ( P=0.0090). Consistent with the underlying concept, renal cell cancer cases who had been exposed to trichloroethylene had higher alpha1-microglobulin excretions than non-exposed cases ( P=0.0005) and also had higher alpha1-microglobulin excretions than exposed controls ( P=0.0004). Of 20 trichloroethylene-exposed renal cell cancer cases only three (15%) displayed a normal alpha1-microglobulin excretion of <5 mg/l. By contrast, 41 (52%) out of 79 non-exposed renal cancer cases showed normal excretions of the biomarker. CONCLUSION: The present data are in agreement with the concept of pathogenesis of renal cell cancers developing under high (suggested: >500 ppm peak exposures) and long-term (several years) exposure to trichloroethylene. They also visualise the potential value of alpha1-microglobulin excretion as a routine biomarker of renal toxicity that may be used in the medical surveillance of trichloroethylene-exposed persons.
Authors: Thomas Mensing; Peter Welge; Bruno Voss; Lüder M Fels; Hajo Hennig Fricke; Thomas Brüning; Michael Wilhelm Journal: Toxicol Lett Date: 2002-03-10 Impact factor: 4.372
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Authors: Ivan Rusyn; Weihsueh A Chiu; Lawrence H Lash; Hans Kromhout; Johnni Hansen; Kathryn Z Guyton Journal: Pharmacol Ther Date: 2013-08-23 Impact factor: 12.310