Kidney Lesions

Renal Effects. Kidney lesions were reported in humans dying of acute methyl parathion (Wofatox) intoxication (Fazekas 1971). See Section S.2.2.2 for a description of these lesions. 

Renal Effects. Hemorrhage of the medullary layer of the kidneys was reported in three persons who died following ingeshon of endosulfan (Terziev et al. 1974). Acute renal failure was a major contributor to the deaths of two individuals who ingested unknown amounts of endosulfan (Blanco-Coronado et al. 1992 Loetal. 1995). In both cases, postmortem examination revealed extensive tubular necrosis. In contrast, no kidney lesions were found in a man who died 4 days after ingesting approximately 260 mg endosulfan/kg (Boereboom et al. 1998). 

Nicholson JK, Osborn D. 1983. Kidney lesions in pelagic seabirds with high tissue levels of cadmium and mercury. J Zool London 200 99-118. 

Nicholson JK, Osborn D. 1984. Kidney lesions in juvenile starlings Stumus vulgaris fed on a mercury-contaminated synthetic diet. Environ Pollut Ser A 33 195-206. 

The mechanism of renal toxicity is not clear. Because the spectrum of kidney lesions observed in male rats (Gorzinski et al. 1985 NTP 1989) resembled those for 2p-globulin nephropathy, hexachloroethane-induced kidney lesions may, in part, be due to hexachloroethane binding to this protein. On the other hand, renal toxicity was observed in female rats and did not present the same sequence of lesions. This suggests the effects in males may not be totally due to 2p-globulin. Specific methods to minimize renal toxicity, based on mechanism of action, cannot be proposed at this time. 

Aminoaciduria, proteinuria and morphological kidney lesions can be induced in rats with a single [420] dose of NiCl2 (2-5 mg Ni/kg intraperitoneally). Amino-acid protein excretions consistently returned to normal by day 5 after exposure. 

No studies were located in humans regarding the distribution of 1,2-dibromoethane after oral exposure. In humans intentionally ingesting 1,2-dibromoethane, kidney lesions and centrilobular necrosis of the liver were found (Olmstead 1960 Saraswat et al. 1986). This is indirect evidence of distribution of 1,2-dibromoethane. The tissue distribution of 1,2-dibromoethane has been studied in rats following exposure by the oral route. Although retention was limited, the kidneys, liver, and spleen appear to retain the highest amounts of the administered dose (Plotnick et al. 1979) as illustrated in Table 2-4. Rats received an oral dose of 15 mg/kg/day of labeled 1,2-dibromoethane in corn oil. Twenty-four hours later 3% of radioactivity was detected in fat, brain, kidney, liver, spleen, testes, blood, and plasma, 72.38% in the urine, and 1.65% in the feces (Plotnick et al. 1979). By 48 hours after administration, 73% of the radiolabeled dose was accounted for in the urine, 1.1% in the liver, and 2.4% in the feces. Total recovery was 77.8% of the administered radioactivity. 

In a study which examined the role of the protein 2. -globulin in 1,4-dichlorobenzene-induced nephrotoxicity in male rats, NCI-Black-Reiter (NBR) rats, known not to S5mthesize the hepatic form of the 2. -globulin, were administered 500 mg/kg/day 1,4-dichlorobenzene by gavage in com oil for 4 consecutive days. Positive controls consisted of Fischer 344 male rats treated with lindane the results were also compared with those obtained in a group of female Fischer 344 rats treated with lindane. End points examined consisted of kidney lesions and protein droplet evaluation. 2.-Globulin was detected in kidney sections from male Fischer 344 rats, but not in male NBR or female Fischer 344 rats. No lesions or hyaline droplets were detected in treated or control male NBR and female Fischer 344 rats (Dietrich and Swenberg 1991). 

Mice exposed to 100 or 50 ppm 6 hour/day, 5 days/week for 2 or 4 weeks developed tubulointerstitial nephritis at the high dose kidney lesions were not observed in the mice exposed to 50 ppm, but histopathologic changes in the nasal mucosa were evident." ... 

In a 2-year inhalation study, rats and mice were exposed to 0, 67, 292, or 2056ppm 6 hours/day, 5 days per week. The major finding was a time- and dose-related increase in the incidence of kidney lesions in the male rats. These lesions consisted of cortical multifocal tubular basophilia (indicative of areas of cell regeneration), protein casts, and interstitial inflammation. There was epithelial cell shedding, and the casts were found within dilated renal tubules commonly at the corti-comedullary junction. 

As with many metals, gold can damage the kidney. Lesions of the mouth and skin are seen following gold therapy to treat arthritis. 

Applieation of 2,3-dibromopropan-l-ol to the skin of rats and miee for 13 weeks caused kidney lesions in male rats, liver lesions in female rats and liver and lung lesions in both male and female miee. 

In the chronic gavage study by NTP (1986), dosed male rats had increased incidences of renal tubular cell hyperplasia, epithelial cell hyperplasia of the renal pelvis, and tubular mineralization. The male rats also had increased incidences of renal tubular cell tumors. The hyperplasia of the tubular cells, therefore, may represent a preneoplastic response (see discussion of cancer below). These proliferative kidney lesions were not observed in male or female mice or in female rats. The mechanism for the induction of proliferative kidney lesions may also be related to a2p-globulin-induced nephropathy (see discussion of cancer below), again raising the question of the relevance of the proliferative kidney lesions in male rats to humans. This issue is presently the subject of scientific investigation. 

Chronic study (mouse) Mammary gland adenocarcinoma, liver necrosis, urinary bladder hyperplasia (640 mg kg-1 per day) Kidney lesions (62.5 mg kg-1 per day)... 

Male and female Swiss-Webster mice were exposed to 60 ppm [240 mg/m ] vinylidene chloride for 4 h (Speerschneider Dekant, 1995). Urine was collected over a 48-h period and animals were then killed. Male mice were more sensitive to vinylidene chloride-induced nephrotoxicity, as assessed by changes in urinary volume, creatinine, glucose and y-glutamyltranspeptidase levels. Increased necrosis was observed in exposed male mice and female mice pretreated with testosterone. Female mice had no observable kidney lesions or alteration in urinary parameters, suggesting the role of CYP2E1 in vinylidene chloride-induced nephrotoxicity. 

Table VIII. Percent mice with kidney lesions by dietary protein and DMH dose...

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