Morphogenesis of decalin-induced renal alterations in the male rat

Abstract

Adult male Fischer 344 rats were killed after 5, 12, 19 or 31 days' ‘occupational’ (6 hr/day, 5 days/wk), ‘semi-continuous’ (22 hr/day, 5 days/wk) or ‘continuous’ (22 hr/day, 7 days/wk) exposure to 125 ppm decalin vapour. Control rats were exposed to filtered air. Kidney sections were evaluated to determine the nature and time-course of development of decalin-induced lesions. The development of renal lesions was characterized by a specific sequence of light microscopically evident alterations. The extent of the alterations was dependent on time and exposure regimen. Severe exacerbation of the spontaneous protein accumulation (hyaline droplets) routinely observed in the kidneys of control male rats was present in kidneys of all decalin-exposed animals at day 5, and was considered to be the primary morphological alteration associated with decalin exposure. The following sequelae of the hyaline droplet response were observed: (1) the variable occurrence of light microscopically evident proximal convoluted tubule (PCT) epithelial cell degeneration/necrosis, presumably a reflection of cellular injury associated with excessive protein accumulation; (2) the occurrence of granular casts at the junction of the inner and outer bands of the outer zone of the medulla secondary to PCT epithelial cell injury; (3) chronic nephrosis, occurring secondary to tubular obstruction by granular casts. This triad of lesions (hyaline droplet accumulation, granular cast formation and chronic nephrosis) lends specificity to the decalin response and establishes a potential mechanistic relationship with other chemicals that induce these effects.