Comparison of short-term renal effects due to oral administration of decalin or d-limonene in young adult male Fischer-344 rats

Kanerva, R.L.; Ridder, Gregg M.; Lefever, F.R.; Alden, Carl L.

doi:10.1016/0278-6915(87)90167-0

Cited by 58 publications

(13 citation statements)

References 11 publications

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“…MON, ETU, and LIM also gave weak increases in liver weight that were sometimes accompanied by liver hypertrophy. Increased liver weight after LIM administration has been shown previously (33). DETU, CEA, and TMTU gave little or no increases in liver weight, but CEA and TMTU did produce liver hypertrophy at later time points.…”

Section: Ratsupporting

confidence: 77%

“…During the early stages of this simulation, we evaluated a range of acute/subacute markers of presumed nongenotoxic rodent carcinogenesis. The markers used in this study have been reported by others for the rodent liver (27,28,30,31,41), kidney (9,26,33,39,40), and thyroid gland (9,37,38). The results of the study for individual markers are shown schematically in Figure 1.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens.

Elcombe

Odum

Foster

et al. 2002

Environ Health Perspect

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We studied nine presumed nongenotoxic rodent carcinogens, as defined by the U.S. National Toxicology Program (NTP), to determine their ability to induce acute or subacute biochemical and tissue changes that may act as useful predictors of nongenotoxic rodent carcinogenesis. The chemicals selected included six liver carcinogens (two of which are peroxisome proliferators), three thyroid gland carcinogens, and four kidney carcinogens. We administered the chemicals (diethylhexyl phthalate, cinnamyl anthranilate, chlorendic acid, 1,4-dichlorobenzene, monuron, ethylene thiourea, diethyl thiourea, trimethyl thiourea, and d-limonene to the same strains of mice and rats used in the original NTP bioassays (nine chemicals to rats and seven to mice). Selected tissues (liver, thyroid gland, and kidney) were collected from groups of animals at 7, 28, and 90 days for evaluation. Tissue changes selected for study were monitored for all of the test groups, irrespective of the specificity of the carcinogenic responses observed in those tissues. This allowed us to assess both the carcinogen specificity and the carcinogen sensitivity of the events being monitored. We studied relative weight, cell labeling indices, and pathologic changes such as hypertrophy in all tissues; a range of cytochrome P450 enzymes and palmitoyl coenzyme A oxidase in the liver; changes in the levels of plasma total triiodothyronine, total thyroxine, and thyroid-stimulating hormone (TSH) as markers of thyroid gland function; and hyaline droplet formation, tubular basophilia, and the formation of granular casts in the kidney. There were no single measurements that alerted specifically to the carcinogenicity of the agents to the rodent liver, thyroid gland, or kidney. However, in the majority of cases, the chemical induction of cancer in a tissue was preceded by a range of biochemical/morphologic changes, most of which were moderately specific for a carcinogenic outcome, and some of which were highly specific for it (e.g., increases in TSH in the thyroid gland and increases in relative liver weight in the mouse). The only measurements that failed to correlate usefully with carcinogenicity were the induction of liver enzymes (with the exception of the enzymes associated with peroxisome proliferation). Most of the useful markers were evident at the early times studied (7 days and 28 days), but no overall best time for the measurement of all markers was identified. The judicious choice of markers and evaluation times can aid the detection of potential nongenotoxic rodent carcinogens.

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Section: Ratsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 96%

Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens.

Elcombe

Odum

Foster

et al. 2002

Environ Health Perspect

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show abstract

“…Then it primarily reaches the lung and may directly affect lung tissues and alveo lar macrophages (MO). On the other hand, there are some reports that terpenoids including D-limonene may irritate the mucous membrane and the skin (14), and further prolonged exposure of D-limonene may result in an impairment of lung function (15)(16)(17)(18) and kidney (19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Distribution and Immune Responses Resulting from Oral Administration of D-Limonene in Rats.

Hamada

Uezu²,

Matsushita³

et al. 2002

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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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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Comparison of short-term renal effects due to oral administration of decalin or d-limonene in young adult male Fischer-344 rats

Cited by 58 publications

References 11 publications

Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens.

Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens.

Distribution and Immune Responses Resulting from Oral Administration of D-Limonene in Rats.

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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