The Urinary System

Gopinath, C.; Prentice, David E.; Lewis, D. J.

doi:10.1007/978-94-009-3189-3_6

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…The initial indication that a chemical may induce α 2u -globulin-related nephropathy is often an observation in 14- or 90-day studies of an increase in hyaline droplets in the tubular epithelium. Droplets are typically seen in control male rats, and increases have resulted from exposures to a variety of hydrocarbons and some pharmaceuticals (Gopinath et al, 1987). These droplets are thought to be largely comprised of α 2u -globulin, and immunoassays have been developed to provide a quantitative measure of renal accumulation.…”

Section: Discussionmentioning

confidence: 99%

α2u-Globulin Nephropathy and Renal Tumors in National Toxicology Program Studies

et al. 2007

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Chemically induced renal neoplasms in male rats, developed coincident with α 2u -globulin nephropathy, are not considered predictive of risk to humans by the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency. Criteria have been defined to establish the role of α 2u -globulin nephropathy in renal carcinogenesis, based on a proposed mode of action involving sustained tubular cell proliferation resulting from α 2u -induced nephropathy, with consequent development of neoplastic lesions. Recent NTP studies demonstrated inconsistencies with this proposed mechanism, including in some cases, far weaker kidney tumor responses than expected based on the extent of α 2u -globulin nephropathy. NTP studies with decalin, propylene glycol mono-t-butyl ether and Stoddard solvent IIC included extended evaluations of α 2u -related nephropathy, and were thus used in assessing the linkage between key events in 90-day studies with renal tumors in 2-year studies. This review revealed no or at best weak associations of tumor responses with renal α 2u -globulin concentrations, indices of cell turnover, or microscopic evidence of α 2u -associated nephropathy in prechronic studies. While tumor responses corresponded somewhat with a measure of cumulative α 2u -associated nephropathy (linear mineralization of the papilla) at the end of the 2-year studies, the severity of chronic nephropathy was generally in best agreement with the pattern of tumor response. These results suggest that while α 2u -globulin nephropathy may contribute to the renal tumor response, the critical component(s) of the nephropathy most closely associated with the development of tumors could not be clearly identified in this review.

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Section: Discussionmentioning

confidence: 99%

α2u-Globulin Nephropathy and Renal Tumors in National Toxicology Program Studies

et al. 2007

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“…8 In this study, the hyaline droplets were seen in both male and female rats in all dose groups, indicating that these droplets are somewhat different from the hyaline droplets usually observed. No adverse effects, such as degeneration or necrosis of tubules or associated clinical pathologic changes, were seen in any of the treated animals.…”

Section: Resultsmentioning

confidence: 48%

Toxic Peripheral Neuropathy with Demyelination in Sprague-Dawley Rats Given CGS 21595 —A 5-Lipoxygenase Inhibitor

Gunson¹,

Sahota²,

Iverson³

et al. 1992

Vet Pathol

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Abstract. Male and female Sprague-Dawley rats were given CGS 21595, a pro-drug that is almost immediately metabolized to CGS 192 13, a naphthoquinone that acts as a 5-lipoxygenase inhibitor. The compound was administered by gavage to five groups of Sprague-Dawley rats (group Nos. 1, 5 , n = 30; group Nos. 2-4, n = 20) at daily doses of 0, 50, 150, 500, or 1,000 mg/kg for 13 weeks. Rats in the higher dose groups had a reduced weight gain, but significant neurologic signs were not observed. A peripheral neuropathy consisting predominantly of myelin destruction in the spinal nerve roots and sciatic nerves was seen in male rats treated with L 150 mg/kg CGS 21 595 and in female rats treated with 2 5 0 mg/kg CGS 21595 for 13 weeks. This lesion was not fully reversible after a recovery period of 4 weeks. Lesions consisted of ballooning of myelin sheaths, infiltration by macrophages, demyelination, and occasional areas of remyelination. Axons were generally preserved, and the brain and spinal cord were not affected. Male and female rats in all treatment groups had cytoplasmic hyaline droplets in the proximal renal tubules. This change was reversible after 4 weeks and was not associated with any other adverse effects on the kidney.

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“…However, this nephropathy was not observed in exposed animals that subsequently underwent a 4-week postexposure period. The characteristics of "light hydrocarbon nephropathy" are increase in kidney weights, the presence of hyaline droplets (alpha-2 ¹ -globulin), and increased incidence and severity of dilated tubules at the corticomedullary junction that may contain granular casts (Alden 1986;Alden and Frith 1991;Gopinath, Prentice, and Lewis 1987). Male rat "light hydrocarbon nephropathy" can be induced by exposure to a diverse group of hydrocarbons.…”

Section: Discussionmentioning

confidence: 99%

Toxicity Evaluation of Petroleum Blending Streams: Inhalation Subchronic Toxicity/Neurotoxicity Study of a Light Catalytic Cracked Naphtha Distillate in Rats

Lapin¹,

Bui²,

Breglia³

et al. 2001

Int J Toxicol

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A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm.

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The Urinary System

Cited by 10 publications

References 24 publications

α2u-Globulin Nephropathy and Renal Tumors in National Toxicology Program Studies

α2u-Globulin Nephropathy and Renal Tumors in National Toxicology Program Studies

Toxic Peripheral Neuropathy with Demyelination in Sprague-Dawley Rats Given CGS 21595 —A 5-Lipoxygenase Inhibitor

Toxicity Evaluation of Petroleum Blending Streams: Inhalation Subchronic Toxicity/Neurotoxicity Study of a Light Catalytic Cracked Naphtha Distillate in Rats

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