Characterization of spontaneous and decalin-induced hyaline droplets in kidneys of adult male rats

Kanerva, R.L.; Ridder, Gregg M.; Stone, L.C.; Alden, Carl L.

doi:10.1016/0278-6915(87)90308-5

Cited by 47 publications

(12 citation statements)

References 32 publications

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“…Recently, droplets showing similar characteristics were observed in the kidneys of rats given decalin, 2,2,4-trimethylpentane, or unleaded gasoline. In these cases, however, they were classified as hyaline droplets (44,46). U2u-Globulin, which is specific for the kidneys of male rats, seems to be involved in the appearance of the hyaline droplets.…”

Section: Subacute Toxicitymentioning

confidence: 90%

Toxicity and Carcinogenicity of Potassium Bromate: A New Renal Carcinogen

Kurokawa¹,

Maekawa²,

Takahashi³

et al. 1990

Environmental Health Perspectives

150

130

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Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.

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Section: Subacute Toxicitymentioning

confidence: 90%

Toxicity and Carcinogenicity of Potassium Bromate: A New Renal Carcinogen

Kurokawa¹,

Maekawa²,

Takahashi³

et al. 1990

Environmental Health Perspectives

150

130

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“…These inclusions in the control rat consist of alpha 2 p globulin, representing a structural and functional protein peculiarity of the male rat in comparison to the female rat, as well as other common laboratory animals or humans. Since the pathologic response to decalin, d-limonene, and unleaded gas has been demonstrated to depend specifically on perturbation of this male rat peculiarity, the predictiveness for humans has been discounted (12,13,19). Since JP-8 creates the same specific spectrum of pathologic response, and since the female rat and mice of either sex did not develop a nephrotoxic response, the predictiveness of the JP-8 hyaline droplet nephropathy for humans should be considered improbable.…”

Section: Discussionmentioning

confidence: 99%

A 90-Day Continuous Vapor Inhalation Toxicity Study of JP-8 Jet Fuel Followed by 20 or 21 Months of Recovery in Fischer 344 Rats and C57BL/6 Mice

Mattie¹,

et al. 1991

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ABSTRAC~The kerosene-type jet fuel, JP-8, consists of a complex mixture of aliphatic and aromatic hydrocarbons. Because of the utility of JP-8, studies have been conducted to identify the potential long-term consequence of occupational inhalation exposure. Fischer 344 rats and C57BLJ6 mice of both sexes were exposed to JP-8 vapors at 0, 500, and 1,000 mg/m3 on a continuous basis for 90 days, then followed by recovery until approximately 24 months of age. Occurrence of necrotizing dermatitis associated with fighting resulted in an increase in mortality in mice (male greater than female) during the 2 week to 9 month post-exposure recovery period. The male rat kidney developed a reversible ultrastructural increase in size and propensity for crystalloid changes of phagolysosomal proteinic reabsorption droplets in the proximal convoluted tubular epithelium. A specific triad of persisting light microscopic renal lesions occurred but functional change was limited to a decrease in urine concentration compared to controls that persisted throughout the, recovery period. The response is comparable to the chronic effect of lifetime exposure of the male rat to unleaded gasoline, d-limonene, and p-dichlorobenzene, except for the absence of tubular tumorigenesis. The active toxicologic response presumably must occur over a greater proportion of the male rat's life span for the tumor component of this male rat hydrocarbon nephropathy syndrome. The predictiveness for humans must be questioned, since the pathologic response to JP-8 involved only one tissue in one sex of one species, and since the male rat response appears to be linked to an inherent renal protein peculiarity.

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“…The proposed sequence ofhistopathological changes is based mainly on research studies with four model substances, unleaded gasoline and TMP (142)(143)(144), decalin (5,6,122,123,145), and dlimonene (123,126). Even for these four substances, not all ofthe individual lesions in the proposed progression have been shown to belong to a sequence ofinterrelated events.…”

Section: U-globulin Nephropathymentioning

confidence: 99%

Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.

Hard

Rodgers

Baetcke

et al. 1993

Environ Health Perspect

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This review paper examines the relationship between chemicals inducing ewessive accumulation of a2u-globulin (ai21g) (CIGA) in hyline droplets inmale rat kidneys and the subsequent development of nephoit and rnal tubule nopaia in the male rt. This dose-responsive hyaline droplet accumulation distinguishes CIGA carcinogens fromclssical renal carcinogens. CIGA carcinogens also do not appear to react with DNA and are generally negative in short-term tests for genotoxicity. CIGA or their metabolites bind specifically, but reversibly, tomale rat a2,-g The resulting complex appears to be more resistant to hydrolytic degradation in the proximaltubule than native, unbound a2,-g Singlecell necrosis of the tubule epithelium, with associated granular cast formation and papillary mineralization, is followed by sustained regenerative tubule cell prolifertin, foci oftubulehyerl a inthe aovoited pronal bules, and renal tubule tumor Although stnrcturally similar proteins have been detected in other species, including hu_ms, renal lesios characteristic Of a2,-g nephropathy have not been observed. Epidemiologic investigation has not specifically examined the CIGA hypothesis for humans. Based on cancer bioassays, hormone manipulation studies, investigations in an ae,-g-deficient strain of rat, and other laboratory data, an increased proliferative response caused by chemically induced cytotoxicity appears to play a role in the development ofrenal tubule tumors in male rats Thus, it is reasonable to suggest that the renal effects induced in male rats by chemicals causing a2.-g accumulation are unlikely to occur in humans. IntroductionFor most hazardous chemicals, adequate human data are not available, and risk analyses must rely on information from laboratory studies of rats or mice. The inference that the results ofanimal experiments can be applied to humans is a fundamental principle of all toxicologic research. This analysis deals with a specific case, however, where the male rat seems to respond in a manner different from other laboratory species. The possibility of a unique response in the rat among laboratory animals raises questions about the applicability of the rat data to other species, including humans. Our review evaluates the matter of human 'Medical Research Council relevance and describes the types of information needed for hazard assessment of such chemicals.A variety of organic chemicals have produced specific renal lesions in male rats in the form of a protein (hyaline) droplet nephropathy accompanied by accumulation of a2%-globulin (a2.-g) [reviewed in (1,2)]. Among the chemicals tested are paraffins (3,4), decalin (decahydronaphthalene) (5,6), petroleum-based and synthetic fuels (7), military aviation propellants (8), and 2,2,4-trimethylpentane (TMP) (9). As seen in Table 1, which lists a sampling ofchemicals that have been tested, many are of considerable regulatory and commercial interest. For example, isophorone is a chemical intermediate of major industrial importance. Aviation and automotive fuels fit i...

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Characterization of spontaneous and decalin-induced hyaline droplets in kidneys of adult male rats

Cited by 47 publications

References 32 publications

Toxicity and Carcinogenicity of Potassium Bromate: A New Renal Carcinogen

Toxicity and Carcinogenicity of Potassium Bromate: A New Renal Carcinogen

A 90-Day Continuous Vapor Inhalation Toxicity Study of JP-8 Jet Fuel Followed by 20 or 21 Months of Recovery in Fischer 344 Rats and C57BL/6 Mice

Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.

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