Kidney effects

Effects of repeated ethylene glycol peroral overexposure in treated rats and mice can result in kidney, Hver, and nervous system damage. The most sensitive indicators of ethylene glycol toxicity are disturbances in acid—base balance and nephrotoxic (kidney) effects. Effects of repeated chronic peroral overexposure of diethylene glycol in treated rats result in kidney and Hver damage (48). 

Toxicity. Breathing moderate amounts of methyl ethyl ketone (MEK) for short periods of time can cause adverse effects on the nervous system ranging from headaches, dizziness, nausea, and numbness in the fingers and toes to unconsciousness. Its vapors are irritating to the skin, eyes, nose, and throat and can damage the eyes. Repeated exposure to moderate to high amounts may cause liver and kidney effects. 

The liver is an organ that shows variable effects from trichloroethylene among species, and this can probably be attributed to interspecies differences in metabolism (see Section 2.4.2.1). Specifically, the apparent difference in susceptibility to trichloroethylene-induced hepatocellular carcinoma between humans and rodents may be due to metabolic differences (see Section 2.4.2.3). Kidney effects are also variable among species. Humans and mice are less sensitive than rats. In rats exposed chronically to trichloroethylene, toxic nephrosis characterized as cytomegaly has been reported (NTP 1988). The kidney effects in rats do not seem to be related to an increase in alpha-2 -globulin (Goldsworthy et al. 1988). Effects on the nervous system appear to be widespread among species, presumably due to interactions between trichloroethylene and neuronal membranes. 

Adverse kidney effects have been reported in rats exposed to lead during development (Fowler et al. 1980). Also, alterations in immune function have been observed in young rats exposed to lead perinatally (Faith et al. 1979 Luster et al. 1978). These studies are discussed in more detail in Sections 2.2.3.2 and 2.2.3.3. 

Intermediate-Duration Exposure. A study (Selden et al. 1994) of 11 workers who wore protective equipment while being exposed to hexachloroethane for 5 weeks showed no respiratory, hematological, liver, or kidney effects at plasma levels of 7.3 + 6 pg/L (Selden et al. 1993). Because mild dermal effects were noted, the principal exposure route may have been dermal. The dermal effects may also have been a result of trauma from the protective equipment. Because of the protective equipment, it is not possible to determine exposure levels. 

It is likely that kidney effects may occur in humans after inhalation or oral exposure to high levels of chloroform however, it is not known whether such effects would occur at the levels of chloroform found in the environment, in drinking water, or at hazardous waste sites. 

Numerous chronic-duration oral studies examined hepatic and renal end points as well as neurological and cancer effects. Serious effects occurred at higher doses 15 mg/kg/day was the lowest dose used in available animals studies. A NOAEL of 2.46 mg/kg/day for liver and kidney effects (SGPT, SGOT, BUN and SAP) was found in humans who used a dentifrice containing 0.34% or a mouthwash containing 0.43% chloroform for 1-5 years (DeSalva et al. 1974). 

Renal Effects. No studies were located regarding renal effects in humans after exposure to 3,3 -dichlorobenzidine by any route. No effects to the kidneys or urinaiy parameters monitored were observed in dogs exposed to 10.4 mg/kg/day for up to 7 years (Stula et al. 1978). Based on these data, it is unlikely that kidney effects will occm in humans exposed to 3,3 -dichlorobenzidine at levels found at hazardous waste sites. 

The mechanisms of action for nephrotoxic (with the exception of 2. -globulin-mediated nephropathy specific to male rats) or hematotoxic effects have not been clearly delineated, and with the available information, it is difficult to speculate how 1,4-dichlorobenzene might cause such effects. More information concerning the mechanisms of action for blood and kidney effects are needed before methods for blocking those mechanism and reducing toxic effects can be developed. 

Several animal studies were located using the oral route for intermediate-duration and based on a combination of these studies, adverse effects have been reported in many organ systems. Hepatic, renal, and hematologic (Bombard et al. 1988 Carlson 1977 Hollingsworth et al. 1956 NTP 1987) effects have been the most consistent observations. The MRL was based on a minimal LOAEL of 188 mg/kg/day based on increased liver weights in rats. Since kidney effects involve hyaline droplet nephropathy, the renal effects were not considered to be a suitable basis for the MRL. 

Exposure of rats to p-dichlorobenzene vapor concentrations up to 538 ppm for 2 generations resulted in Fq and Fi adult toxicity, including reduced body weights in both sexes and kidney effects (hyaline droplet neuropathy and renal tubular cell hyperplasia) in males, but... 

Scala RA Comments on Structure-Activity Relationships, Summary and Concluding Remarks, pp IM. Unpublished addendum to Workshop on the Kidney Effects of Hydrocarbons. Boston, 1984... 

Rats fed 62 mg/kg/day for 16 weeks exhibited no overt toxicity. Kidney effects characterized by increased kidney weights and microscopic changes (tubular atrophy, degeneration, hypertrophy and/or dilation) were observed in males at 15 and 62 mg/kg/day in females tubular atrophy and degeneration of the kidneys were observed only at the highest dose. Both sexes also had increased liver weights at 62 mg/kg/day. ... 

Male and female rats fed diets containing 0.01%, 0.05%, 0.25%, or 1.25% for 90 days showed histologic evidence of liver and kidney effects at the highest level. ... 

No data were located on the effects of acute-duration oral exposure in humans. Two studies are available on the acute oral toxicity in animals. A LOAEL value of 4 mg/kg/day (based on kidney effects) was reported in one study in rats exposed to hexachlorobutadiene for 14 days (Harleman and Seinen 1979). On the other hand, a NOAEL value of 10 mg/kg was reported for kidney effects in a 24-hour rat study (Jonker et al. 1993a). Neither of these studies was considered suitable for the... 

No data were located on the effects of chronic-duration exposure in humans. A chronic-duration study in animals revealed tubular hyperplasia in rats at dose levels of 2 mg/kg/day or greater (Kociba et al. 1977a), but not at 0.2 mg/kg/day, the LOAEL for kidney effects from the intermediate-duration study in mice. Because the intermediate-duration MRL protects against chronic exposures, a chronic MRL has not been proposed. 

In the Hazleton Labs (1968) 4-week study, no treatment-related histopathological effects on the kidney were found in rats exposed to 37 ppm. Because the histological examination was performed on only 30% of the treated and control rats, however, the possibility exists that renal lesions were missed. The 37 ppm concentration can be considered an intermediate duration NOAEL for kidney effects, however, because no exposure-related renal effects were detected upon urinalysis and histological examination of rats and rabbits that were exposed to isophorone in air at a concentration of 250 ppm for 18 months (Dutertre-Catella 1976). The NOAELs of 37 ppm for intermediate duration and 250 ppm for chronic exposure are presented in Table 2-1 and Figure 2-1. 

Isophorone produced kidney effects in male rats in the NTP (1986) study. Strasser (1988) found that isophorone caused protein droplet formation in the kidneys of male rats, suggesting that isophorone can induce protein nephropathy. Alden (1986) discussed the possibility that proteinuric humans and humans with low molecular weight protein nephropathy, such as people with multiple myeloma (Bence-Jones protein) or mononuclear cell leukemia (lysozyme), may be more susceptible to chemically-induced protein nephropathy. He concluded, however, that this syndrome is probably specific to the male rat. 

Welch W3 Adenosine Al receptor antagonists in the kidney Effects in fluid-retaining disorders. Curr Opin Pharmacol 2002 2(2) 165. [PMID 11950628]... 

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