Hyaline droplet nephropathy

Male rats are sensitive to renal tubular nephropathy after exposure to hexachloroethane. The lesions observed are characteristic of hyaline droplet nephropathy. They are most likely the result of hexachloroethane or one of its metabolites binding to the excretory protein 2p-globulin, altering its kidney transport, and leading to the formation of hyaline droplets. This protein is synthesized by male rats and accounts for 26% of their urinary protein excretion (Olson et al. 1990). It is not excreted in female rats except in minimal quantities. Since some effects are also seen in kidneys of female rats and in male and female mice that do not synthesize 2p-globulin, hexachloroethane must also have milder adverse effects on the kidney through a different mechanism. 

Chronic-Duration Exposure and Cancer. No studies were located in humans following chrome-duration exposure to hexachloroethane for any exposure route. No chronic animal studies were conducted using the inhalation route of exposure. In oral studies with rats, the kidney was identified as a primary target organ in males and females (NTP 1989). The kidney damage in male rats was the result of hyaline droplet nephropathy and, accordingly, was not suitable as the basis for an oral MRL. In contrast to acute- and intermediate-duration oral exposure, liver toxicity was not evident in rats following chronic oral exposure. There were no studies of chronic dermal exposure to hexachloroethane. 

Olson MJ, Johnson JT, Reidy CA. 1990. A comparison of male rat and human urinary proteins implications for human resistance to hyaline droplet nephropathy. Toxicol Appl Pharmacol 102 524-536. 

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... 

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. 

Male rats administered 0.62 or 1.24mmol/kg per day by gavage for 21 days showed hyalin droplet nephropathy. ... 

Gavage administration of 0.62 or 1.24 mmol/%/day to rats for 21 days did not cause clinical signs of toxicity or microscopic effects in either the liver or kidney. The inability to produce hyalin droplet nephropathy suggests that kidney neoplasms would not occur in rats in 2-year studies. ... 

Rats exposed to an aerosol of diesel fuel no. 2 at 100 mg ml demonstrated very mild histological changes in the liver and thyroid. No other biochemical effects, hematological effects, or tissue changes were observed in the exposed animals. Continuous 90 day inhalation exposure to 50 or 300mgm" of marine diesel fuels produced hyaline droplet nephropathy and reduced body weight gain in male rats. 

Several inhalation studies with Stoddard Solvent have shown that male rats develop hyalin droplet nephropathy which is believed to be associated with the a-2u-globulin in male rats. Stoddard Solvent did not cause developmental toxicity based on studies in rats. 

Murty CVR, Olson MJ, Garg BD, et al. 1988. Hydrocarbon-induced hyaline droplet nephropathy in male rats during senescence. Toxicol Appl Pharmacol 96 380-392. 

A number of chemicals of diverse structure have been shown to produce a specific form of nephropathy in male rats but not in female rats or mice of either sex. The histological features of this syndrome, which has been called a2u-globulin nephropathy or hyaline droplet nephropathy, are the excessive accumulation of eosinophilic, hyaline droplets in epithelial cells of the P2 segment, an increase in... 

Lehman-McKeeman, L. D., and Caudill, D. (1992b). Biochemical basis for mouse resistance to hyaline droplet nephropathy Lack of relevance of the alpha 2u-globulin protein superfamily in this male rat-specific syndrome. Toxicol Appl Pharmacol 112, 214-221. 

Hard GC, Rodgers IS, Baetcke KP, Richards WL, McGaughyRE, Valcovic LR (1993) Hazard evaluation of chemicals that cause accumulation of a2u-glohulin, hyaline droplet nephropathy, and tuhule neoplasia in the kidneys of male rats. Environ Health Perspect 99 313-349... 

Henningsen GM, Yu KO, Salomon RA, et al. 1987. The metabolism of f-butylcyclohexane in Fischer-344 male rats with hyaline droplet nephropathy. Toxicol Lett 39 313-318. 

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