Renal lesions

Renal Effects. Hemorrhage of the medullary layer of the kidneys was observed in an early report of three fatal cases of acute oral poisoning with endosulfan (Terziev et al. 1974). More recent studies have reported acute renal failure after ingestion of endosulfan as a major contributing cause of death in two individuals in both cases, postmortem examination showed extensive tubular necrosis (Blanco-Coronado et al. 1992 Lo et al. 1995). Neither case discussed the possible mechanism of endosulfan-induced acute renal failure, but in one case, the authors of the report indicate that the renal lesions may relate to sepsis and shock (Blanco-Coronado et al. 1992). Ingested doses were not determined in any of these cases, and it is not totally clear that the effects observed at autopsy were a direct result of endosulfan exposure, although based on results from acute animal studies, it seems likely. 

Chronic exposure of both rats and mice resulted in tubular nephropathy in both males and females. In rats, lesions were present in 45-66% of the males when they were sacrificed at 110 weeks after receiving 212 and 423 mg/kg/day hexachloroethane for 66 weeks of a 78-week exposure period (NTP 1977 Weisburger 1977). The renal lesions were characterized by hyperchromic regenerative epithelium, necrosis, interstitial nephritis, fibrosis, focal pyelonephritis, tubular ectasis, and hyaline casts. Lesions were also present in females but had a lower incidence (18% and 59%) for the two dose groups. Two-year exposures of male rats to much lower doses (10 and 20 mg/kg/day) resulted in similar effects on the kidneys (NTP 1989). Minimal to mild nephropathy was present in females for doses of 80 and 160 mg/kg/day. Over 90% of the male and female mice exposed to 590 and 1,179 mg/kg/day hexachloroethane for 78 weeks displayed tubular nephropathy when sacrificed at 90 weeks (NTP 1977 Weisburger 1977). Regenerative tubular epithelium was visible and degeneration of the tubular epithelium occurred at the junction of the cortex and the medulla. Hyaline casts were present in the tubules, and fibrosis, calcium deposition, and inflammatory cells were noted in the kidney tissues. 

Acute-, intermediate-, and chronic-duration oral exposures of male rats to doses of 10 mg/kg/day or greater were associated with renal tubular nephropathy (Gorzinski et al. 1985 NTP 1977, 1989 Weeks et al. 1979). Affected animals displayed tubular necrosis, hyaline droplets in tubular epithelial cells, regenerative tubular epithelium, interstitial nephritis, and fibrosis. The severity of the renal lesions varied with the dose and the duration of exposure. 

Renal Effects. No studies were located regarding renal effects of mirex or chlordecone in humans. However, studies in animals indicated an increase in the severity of renal lesions observed in rats... 

Renal Effects. Renal lesions have been reported in humans dying acutely after acute oral exposure... 

Renal lesions or changes in renal function in humans chronically exposed to 1,2-dibromoethane have not been identified. Following chronic inhalation exposure to 1,2-dibromoethane, rats developed toxic nephropathy (NTP 1982). 

Chan WL, Tang NL, Yim CC, et al. New features of renal lesion induced by stroma free hemoglobin. Toxicol Pathol 2000 28 635. 

These observations of renal effects in female rats and in mice of both sexes are important because they provide evidence that renal lesions in response to 1,4-dichlorobenzene exposure are not limited to male rats and do not require the presence of high levels of the renal protein of 2. -globulin. Therefore, although humans may not be at risk for certain 1,4-dichlorobenzene-induced renal lesions (renal hyaline droplet nephropathy), they are possibly at risk for others. However, it is unlikely that levels of... 

Voles M.pennsylvanicus) suffer renal lesions (interstitial nephritis) when fed extracts of white clover, T. repens. Milder lesions were observed after feeding on reed phalaris Phalaris arundinacea) and timothy Phleum pratense). Many varieties of reed phalaris contain the toxic compoimds gramine and tryptamine (Fig.11.15). In summer and autumn, protein levels in the leaves decrease, fiber content goes up, and secondary compoimds increase in concentration. Therefore, second growth plants have more toxic effects on voles than the spring plants that grow fast and have lower levels of secondary compounds (Bergeron etal, 1987). 

Renal lesions have been produced in mice by dermal application of JP-5 or marine diesel fuel. The inability to duplicate these lesions with intraperitoneal administration suggested that skin application, in particular the alteration of skin following repeated dermal application, was necessary to produce the renal toxicity, and that the renal effects appeared to be secondary to skin injury (Easley et al. 1982). Lymphocytic inflammation has been induced in the urinary bladder of mice with chronic dermal application of JP-5 or marine diesel fuel (NTP/NIH 1986). However, acute and intermediate dermal exposures to kerosene and JP-5, respectively, were not toxic to the renal system of mice (Upreti et al. 

Administered by oral gavage to rats for 6 months, all three isomers produced splenic lesions. The meta and para isomers produced testicular atrophy, whereas o/t/ o-nitrotoluene caused renal lesions. ... 

Hypersensitivity reactions are rare, they consists of fever, skin reactions, bone-marrow depression and sulfonamide like renal lesions. 

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. 

Marzotko, D. Pankow, D. (1988) Renal lesions following dichloromethane intoxication. Z mikrosk.-anat. Forsch, 102, 461-469... 

Reznik, G, Reznik-Schuller, H.M., Rice, J.M. Hague, B.F. (1981) Pathogenesis of toxic and neoplastic renal lesions induced by the flame retardant tris(2,3-dibromopropyl)phosphate in F344 rats, and development of colonic adenomas after prolonged oral administration. Lab. Invest., 44, 74-83... 

Poulos BK, Perazzolo M, Lee MY, et al. 1996. Oral aluminum administration during pregnancy and lactation produces gastric and renal lesions in rat mothers and delay in CNS development in their pups. Mol Chem Neuropathol 29 15-25. 

The renal lesions which have been described in idiopathic hypercalcemia are not specific. Similar changes have been observed in hyperchloremic renal acidosis of infancy (B7, D7), in various other diseases of infancy and in hypervitaminosis D. It is interesting to note that a recent re-examination of the histological sections of Thatcher s cases of a quarter of a century ago showed that the changes there were essentially the same as those occurring in idiopathic hypercalcemia of infancy (Rl). 

The kidneys (Table VIII) appeared less sensitive to DMH toxicity than liver. Renal lesions consisted of focal, usually subscapular fibrosis with atrophy and hyperplasia of tubular epithelium and variable inflammatory infiltrates. This lesion was designated "interstitial nephritis" or "pyelonephritis" when the renal pelvis was involved. There was no statistical basis for differentiating the lesion with involvement of the pelvic from that without, and therefore the two designations have been pooled for... 

Renal effects observed in animals following oral barium exposure have been minor. Increased kidney/body weight ratios have been noted in rats exposed acutely by gavage to 198 mg barium/kg/day as barium chloride however, this change was not associated with gross or microscopic renal lesions (Borzelleca et al. 1988). 

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