Renal toxicity after chronic inhalation exposure of rats to trichloroethylene
Introduction
Exposure to high levels of trichloroethylene (TRI) may cause neurotoxic, hepatotoxic and/or nephrotoxic effects (Kaneko et al., 1997, Brüning and Bolt, 2000).
An increased incidence of renal cell carcinoma in workers exposed to high concentrations of TRI has been reported (Vamvakas et al., 1998). Chronic tubular damage has been addressed as a prerequisite for the development of renal cell cancer in exposed workers (Brüning et al., 1996) and the release of specific markers for the tubular damage after TRI exposure was reported (Brüning et al., 1999). The human nephrocancerogenicity of TRI has been discussed controversely (Mandel, 2001, Brüning and Bolt, 2000, Vamvakas et al., 1998).
Most experimental chronic inhalation studies have reported only cancer endpoints (Barton and Clewell, 2000). However, Chakrabarti and Tuchweber (1988) have demonstrated a nephrotoxic potential of TRI in F344 rats after exposure to high TRI concentrations, leading to inreased urinary release of proteins and NAG.
In the present study, nephrotoxic effects of TRI after chronic inhalation exposure to a high concentration of 500 ppm were examined. An exposure period of 6 months was chosen to study nephrotoxic effects. The aim of the study was to concurrently examine the internal exposure, functional and morphological alterations, and genotoxic effects.
Metabolites of the oxidative pathway, trichloroacetic acid (TCA) in urine and trichloroethanol (TCE) in blood, were determined for biomonitoring. Marker excretion related to specific kidney damage was determined in urine. Histological examinations were performed and possible genotoxic effects were examined by using the single-cell gel electrophoresis (‘comet assay’).
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Material and methods
Male Long-Evans rats (LE/Mol; M&B, Ry, Denmark) were used in the study. At the beginning of exposure, animals weighed 270±18 g. The animals were housed in a 12 h dark–light cycle and had access to a standard diet (Altromin 1324, Altromin, Lage, Germany) and to water ad libitum.
Exposures to 0 or 500 ppm TRI were conducted in two identical stainless chambers (Ebeco, Castrop-Rauxel, Germany), at the same time. Rats were exposed groupwise in separate cages of stainless wire. Humidity (55±8%) and
Results
TCA values in the urine of exposed rats ranged between 327 and 2577 mg/l. TCA values in the controls ranged from below detection limit to 15.5 mg/l; the mean value (±standard deviation) for exposed animals (n=38) was 1220±610 mg/l, and <3 mg/l for the controls (n=37; P<0.0005). The median of TCE concentration in blood of exposed animals (n=13) was 110 μg/l (Range: 0–260 μg/l) versus <50 μg/l (P<0.005) in controls (n=11).
The results of the urinary marker (HMW, ALB, NAG, and LMW) determinations
Discussion
An increased release of urinary markers for renal damage appeared in TRI exposed rats. The TCE levels in blood and TCA levels in the urine indicated the internal exposure associated with the repetitive external exposure to 500 ppm TRI.
The control values for total protein, creatinine and NAG in the urine of non-exposed rats were at the same level as reported by Green et al. (1998). However, we detected significant elevated values in the release of markers of a tubular damage (NAG and LMW),
Acknowledgements
We thank Professor J. Angerer and Dipl.-Ing. K.H. Schaller (Friedrich-Alexander University, Erlangen-Nürnberg, Germany) for trichloroethanol determinations, Professor K.-M. Müller for support with the histopathology of the renal tissues, and the HVBG (Hauptverband der gewerblichen Berufsgenossenschaften) for financial support. The authors are grateful to S. Böhm, A. Bracht, S. Schuchardt and P. Wieskämper for excellent technical assistance.
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