The Liver

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

doi:10.1007/978-94-009-3189-3_4

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…30 Special Issue (Gopinath et al, 1987;Greaves, 1990a). It is thus assumed that this change was related to increases observed in various metabolizing enzyme activities in this study.…”

Section: Figmentioning

confidence: 74%

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

et al. 2005

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-A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases in T3 and/or T4 in both sexes and generations at 300 ppm were presumed to be secondary changes associated with the induction of hepatic drug-metabolizing enzymes. Blood hormone analysis revealed no changes in sex hormones attributable to lindane in males or females. Hepatic drug-metabolizing enzyme activities were increased dose-dependently from 10 ppm in both sexes and generations, with the rise in BROD activity being the most prominent. There were also increases in MROD, EROD, T-6β-OH, and T4-UDP-GT activities (BROD >> EROD > MROD, T-6β-OH, T4-UDP-GT). This suggests that while lindane most strongly induces CYP2B, it also upregulates a number of other drug metabolizing enzymes, such as CYP1A, CYP3A, and UDP-GT. As for effects on reproductive function, lack of maternal behavior, including lactation and retrieval behavior, and consequent total litter loss were observed in F1 dams at 300 ppm. There were no effects of lindane on the estrous cycle, spermatogenesis, mating, fertility, pregnancy, or parturition. Neonatal toxicity was observed in bot...

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“…30 Special Issue (Gopinath et al, 1987;Greaves, 1990a). It is thus assumed that this change was related to increases observed in various metabolizing enzyme activities in this study.…”

Section: Figmentioning

confidence: 74%

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

et al. 2005

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“…Aortic aneurysms and ruptures can be induced in rodents by various xenobiotics such as β-aminopropionitrile, 20,21 high zinc doses, 20 cysteamine (β-mercaptoethylamine), 22 and angiotensin II. 23 Rats exposed in utero to semicarbazide or N -(2-aminoethyl) ethanolamine develop dissecting aortic aneurysms.…”

Section: Discussionmentioning

confidence: 99%

Idiopathic Aneurysms of the Ascending Aorta in the Mouse and Rat

et al. 2021

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Aneurysms of the ascending aorta, unrelated to xenobiotic administration, are described in 5 rats and 2 mice in nonclinical safety studies conducted at Charles River Laboratories (CRL) sites over the past 10 years. The most prominent microscopic finding was focal dilation with disruption of the wall of the ascending aorta with chronic adventitial inflammation or fibroplasia. The pathogenesis of this finding is unknown. There were no associated macroscopic findings, clinical abnormalities, or vascular lesions elsewhere. The results of a search of historical control data from toxicology studies of 1 day to 72 weeks’ duration performed at CRL for aortic findings from 5900 mice and 23,662 rats are also reported. Aortic lesions are uncommon in mice and rats used in nonclinical safety studies, but toxicologic pathologists should be aware that aneurysms of the ascending aorta with fibroplasia and inflammation in the aortic wall and adventitia may occur spontaneously or iatrogenically, as they have the potential to impact interpretation in toxicology studies.

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“…Hepatocyte vacuolation is a common background change in rats which are not exsanguinated at necropsy and where there is a delay between death and removal of the liver. hyperplasia in which the bile duct epithelium assumes the characteristics of intestinal epithelium and produces large cystic areas filled with mucus (Gopinath 1987). 2.73) causing nodular protrusions on the anterior surface of the liver are associated with small diaphragmatic hernia.…”

Section: Liver and Biliary Systemmentioning

confidence: 99%

Wistar and Sprague–Dawley rats

McInnes¹

2012

Background Lesions in Laboratory Animals

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The Liver

Cited by 7 publications

References 28 publications

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

Idiopathic Aneurysms of the Ascending Aorta in the Mouse and Rat

Wistar and Sprague–Dawley rats

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