Nephrotoxic Chemical Mixtures

Given the almost constant exposure of humans to toxic chemicals (via air pollution, water pollution, or food contamination) and the filtration function of the kidneys, one could easily argue that the kidneys are almost constantly exposed to mixtures of toxic chemicals and that the uptake of additional xenobiotic chemicals creates new mixtures. As we have already seen earlier, many single chemicals have been shown to be renal toxins. Whether the observed nephrotoxic effects of any of these chemicals are because of its interactions with endogenous or other exogenous chemicals is unknown. What is known is that exposures to some chemical mixtures are toxic to the kidneys of test animals and humans. Examples of studies demonstrating mixture effects follow  

JP-8 jet fuel is a complex mixture of primarily C8-20 aliphatic and aromatic hydrocarbons. Those living near airports and military aviation training sites are exposed to the volatile fraction of JP-8 by inhalation. Laboratory rats exposed via inhalation to JP-8 jet fuel vapors were shown to have protein alterations in their kidneys. 

Laboratory animals were exposed to a mixture of chlorinated hydrocarbons at concentrations found in underground water near an electronic appliances factory in Taiwan. The mixture consisted of 

Though the exposures were to low levels of all chemicals, the exposed animals experienced multiple system effects, including increased kidney weights)9 

Chloroform, dichloroacetic acid, and trichloroacetic acid are disinfection byproducts of water chlorination. In a study of laboratory rats it was shown that both dichloroacetic acid and trichloroacetic acid increase the renal toxicity of chloroform in test animals J10l 

---

Exposures to chemical substances such as carbon tetrachloride, 1,1-dichloroeth-ylene, paradichlorobenzene, ethylbenzene, monochlorobenzene, tetrachloroethyl-ene, toluene, 1,1,2-trichloroethane, xylenes, cadmium, and lead are known to canse adverse effects on the kidney. The kidney is unusually susceptible because of its role in filtering harmful substances from the blood. Some of these toxicants canse acnte injury to the kidney, while others produce chronic changes that can lead to end-stage renal failure or cancer. Furthermore, evaluation of the nephrotoxicity of complex industrial waste mixtures with organic chemicals and metals reqnires more stndies. 

As filtering organs, the kidneys are almost constantly exposed to mixtures of toxic chemicals and their metabolites. Many single chemicals are nephrotoxic, but it is not always clear whether or not their toxicity is enhanced by interaction with endogenous or exogenous chemicals. Laboratory animal studies, however, have demonstrated and human observations have observed that the kidneys are subject to unanticipated toxic effects when living beings are exposed to mixtures of toxic chemicals. 

---