Nephrotoxicity occupational exposures

Renal Effects. Occupational exposure to silver metal dust has been associated with increased excretion of a particular renal enzyme (N-acetyl-p-D glucosaminidase), and with decreased creatinine clearance (Rosenman et al. 1987). Both of these effects are diagnostic of marginally impaired renal function. However, the workers in this study were also exposed to cadmium, which was detected in the urine of 5 of the 27 workers studied. Cadmium is known to be nephrotoxic differentiation of the effects of the two metals in the kidney is not possible with the data presented. Therefore, no conclusion can be drawn regarding renal effects of silver based on this study. 

Price RG, Taylor SA, Chivers I et al. (1996) Development and validation of new screening tests for nephrotoxic effects. Hum Exper Toxicol 15 S10-S19 Price RG, Berndt WO, Finn WF et al. (1997) Urinary biomarkers to detect significant effects of environmental and occupational exposure to nephrotoxins, III. Minimal battery of tests to assess subclinical nephrotoxicity for epidemiological studies based on current knowledge 19 535-552 Price RG (2000) Urinalysis to exclude and monitor nephrotoxicity. Clin Chim Acta 297 173-182 Price RG (2002) Early markers of nephrotoxicity. Comp Clin Pathol 11 2-7... 

Occupational exposure to inorganic germanium compounds can cause slightly impaired renal function (2). However, severe nephrotoxic reactions have been described, and it has become clear that these can occur both with inorganic and organic germanium compounds (SEDA-21, 235). 

Figure 1 Overview of trace elements and metals that may either be nephrotoxic after environmental or occupational exposure or of whom the concentration may be disturbed in patients already having chronic renal failure.

It should be noted that in the majority of the above mentioned studies, metal-induced renal injury was considered as if exposure occurred to only one metal at a time. In reality it is clear that environmental and occupational exposure may involve several metals at the same time and in varying concentrations [34]. It has been shown that with combined exposure various metals may interact with each other and that one metal may alter the potential toxicity of another in either a beneficial or deleterious way. As an example, whilst arsenic has been shown to worsen cadmium-induced nephrotoxicity, data from experimental studies have shown that selenium may protect against the renal effects induced by cadmium [52]. Other studies have shown that the iron status may alter the toxic effects of aluminium at the level of the bone and the parathyroid gland [53,54], whilst in a recent increased lead accumulation was associated with disturbances in the concentration of a number of essential trace elements [55]. 

Trichloroethylene is a versatile chemical compound used extensively in vapour degreasing of metals, and to a more limited degree, as a solvent for dry-cleaning and for adhesives. Although the major rate of elimination of trichloroethylene, regardless of the method of exposure, in the rat is by exhalation through the pulmonary system (Daniel 1963), in man the nephrotoxic and genotoxic N-acetyl-S-dichlorovinyl-L-cysteine as an urinary metabolite was found after occupational exposure to 1,1,2-trichloroethylene (Birner et al. 1993). 

Bimer G, Vamvakas S, Dekant W, et al. 1993. Nephrotoxic and genotoxic N-acetyl-S-dichlorovinyl-L-cysteine is a urinary metabolite after occupational 1,1,2-trichloroethene exposure in humans Implications for the risk of trichloroethene exposure. Environ Health Perspect 99 281-284. 

The main targets of heavy metal toxicity are the kidneys and central nervous system. In humans, occupational or environmental exposure of inorganic heavy metals is known to be nephrotoxic at relatively high levels of exposure, with numerous reports of tubulointerstitial nephritis possibly... 

Roels HA, Hoet P, Lison D. Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity. Ren Fail. 1999 May-Jul 21(3-4) 251-62. 

In the search for a role for such exposure, the following questions need to be answered (i) does occupational/environmental exposure to a potential nephrotoxic substance play a direct etiological role in the induction of a particular renal disease, (ii) does the exposure correlate with an increased risk for the progression of renal damage already present in patients with glomerulonephritis, diabetic nephropathy, hypertensive renal disease etc. (iii) dobothpossibihties have to be considered concomitantly or separately ... 

Cardiovascular effects of Pb in humans are the subject of Chapter 13, particularly with respect to effect potency in older exposure subjects but with inclusion of other risk groups. Cardiovascular effects, while inconsistently quantified across human populations, have been identified in multiple epidemiological studies, supported by a number of experimental data sets appearing in the global literature. Chapter 14 on human reproductive and developmental impacts of lead exposures presents the more useful data across several risk groups within human populations. Chapter 15 discusses adverse effects of lead on the renal system as nephrotoxicity is considered to occur across both occupational and nonoccupational subsets of human populations and subsets within nonoccupational categories. Discussions in Chapter 15, much like those in Chapter 18 on immunotoxicity, have benefited from quite recent findings. 

This chapter describes the acute and chronic nephrotoxic effects of lead in human populations. These effects have long been recognized in chronic adult occupational lead exposures and in nonoccupational adult exposures arising from dietary Pb intakes, producing disorders such as gouty nephropathy. In acute childhood Pb exposure, severe kidney effects in the form of Fanconi syndrome were identified in the early pediatric literature. The syndrome often co-occurred with acute encephalopathy. 

Lead exposures in diverse human populations produce both acute and chronic nephrotoxic effects. The chronic kidney disease association with occupational Pb exposures in the clinical literature, dating to the nineteenth century, was typically characterized as a glomerulonephritic disease histo-pathologically. This traced to the absence of evaluation of the temporal course of Pb-induced nephropathy, particularly the acute effects. 

The very low mean PbBs in these women and those men and women in the Muntner et al. (2003) U.S. NHANES III provided good evidence that the relative threshold for Pb nephrotoxic effects with environmental exposures in the general population is an order of magnitude less than was observed in the older occupational Pb literature, 60 pg/dl. Low body lead burdens indexed as chelatable Pb amounts of <80 pg/dl were also found to be a predictor of decreased kidney function (Lin et al., 2006). Taiwanese chronic kidney disease patients (N = 108) without diabetes were assigned to chelation and nonchelation groups. Those patients who were not periodically chelated over a 24-month testing period sustained a mean reduction in GFR of 4.6 ml/min/1.732 m and showed increased serum creatinine. 

Nephrotoxicity Yes, to include lower exposures Environmental and occupational populations Yes Yes Yes... 

Dudley RE, Klaassen CD (1984) Changes in hepatic glutathione concentration modify cadmium-induced hepatotoxicity. Toxicol Appl Pharmacol 72 530-538 Dudley RE, Svoboda DJ, Klaassen CD (1982) Acute exposure to cadmium causes severe liver injury in rats. Toxicol Appl Pharmacol 65 302-313 Dudley RE, Gammal LM, Klaassen CD (1985) Cadmium-induced hepatic and renal injury in chronically exposed rats likely role of hepatic cadmium-metallothionein in nephrotoxicity. Toxicol Appl Pharmacol 77 414-426 Dunphy B (1967) Acute occupational cadmium poisoning a critical review of the literature. J Occup Med 9 22-26... 

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