Atlas of Experimental Toxicological Pathology

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

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

Cited by 90 publications

(61 citation statements)

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“…After 28-day repeat administration, safrole induced decrease of body weight and increase of absolute and relative liver weight and reduced ALP level and increased AST and ALT levels with eosinophilic change, single cell necrosis and hypertrophy of hepatocytes. This is in line with the report that drug-metabolizing enzymes are induced by safrole treatment (Greaves et al, 1990), with hypertrophy of hepatocytes often observed as a biological adaptive response (Gopinath et al, 1987). Photo 1 shows a typical example of histopathological changes Fig.…”

Section: Resultssupporting

confidence: 89%

“…From animal studies, safrole has been classified as a weak hepatocarcinogen (Miller et al, 1983), with effects attributable to formation of safrole-DNA adducts following hepatic cytochrome P450 biotransformation to 1'-hydroxy-safrole. It has been reported that drug-metabolizing enzymes are induced by safrole treatment (Greaves, 1990) and hypertrophy of hepatocytes is often observed as a biological adaptive response (Gopinath et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

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Optimization of an Animal Test Protocol for Toxicogenomics Studies (Ii); A Cross-Laboratory Gene Expression Analysis

et al. 2007

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-Toxicogenomics is a promising new tool for prediction of chemical toxicities including carcinogenicity in a relatively short period. However, it is important to develop a reliable animal test protocol for toxicogenomics studies. The preparation of RNA and tissues is also crucial, since it greatly influences outcomes of gene expression analysis.We proposed an animal test protocol for toxicogenomics studies. In the present study, we examined an animal test protocol by comparing biological and gene expression data from different laboratories running identical in vivo studies on the same microarray platform. The results gave good correspondence in all three laboratories at the level of biological responses and gene expression, especially for genes whose expression changes were quite large. As the fold change or the signal values become smaller, however, discrepancies occur in gene expression data. For example, one laboratory shows an opposite directional change to the other two or no change. The results of hierarchical clustering and principal component analysis (PCA) demonstrated all samples from the three laboratories being clearly divided between control and treatment.Examination of the reproducibility of gene expression data across laboratories using the proposed animal test protocol thus confirmed only minor differences, which was expected to present no problems for gene expression analysis.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Optimization of an Animal Test Protocol for Toxicogenomics Studies (Ii); A Cross-Laboratory Gene Expression Analysis

et al. 2007

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“…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 immuno-assays 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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“…The changes consisted of eosinophilic inclusions in the olfactory epithelium and foci of necrosis of the ventral cartilage in the larynx. The presence of increased numbers of eosinophilic inclusions in olfactory epithelium is a relatively common nonspecific reaction to a mildly irritant material (Gopinath et al, 1987). These inclusions have been reported with dimethylamine, ozone, and chlorine (Lewis et al, 1994;Wolf et al, 1995).…”

Section: Discussionmentioning

confidence: 98%

Twenty-Eight-Day Repeated-Dose Inhalation Exposure of Rats to Diethylene Glycol Monoethyl Ether

Hardy¹,

Coombs²,

Lewis³

et al. 1997

Toxicol Sci

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This study was carried out to provide information on the effects of inhalation of diethylene glycol monoethyl ether, a substance used in industry which may be accidentally inhaled by man. Sprague-Dawley CD rats were exposed by inhalation to a test atmosphere containing diethylene glycol monoethyl ether in a nose-only exposure system for 6 hr a day, 5 days a week for 28 days. Mean exposure levels were 0.09, 0.27, and 1.1 mg/liter. At the two lowest exposure levels the test substance was present entirely as vapor, but at the highest exposure level the test atmosphere was approximately equally divided by mass into respirable droplets (aerosol) and vapor. A comprehensive battery of toxicological evaluations including food consumption, body weight, clinical signs, hematology, and biochemistry revealed no evidence of a systemic effect of exposure. Histopathologica] examination showed changes indicative of mild nonspecific irritation in the upper respiratory tract of rats exposed at the two highest exposure levels. These changes consisted of foci of necrosis in the ventral cartilage of the larynx of rats exposed at 0.27 or 1.1 mg/liter and an increase in eosinophilic inclusions in the olfactory epithelium of the nasal mucosa of rats exposed at 1.1 mg/liter. The no observed adverse effect level for systemic effects was 1.1 mg/liter and the no observed adverse effect level for signs indicative of mild nonspecific irritation of the upper respiratory tract was 0.09 mg/liter. c 1997 sodoy of Toxicology.Diethylene glycol monoethyl ether (DEGEE) (Cas No. 111-90-0) is a colorless liquid with a mild, pleasant odor. This material is widely used as a solvent in industry where, in common with other glycol ethers, its miscibility with water and organic solvents makes it particularly useful as a cosolvent in many oil/water compositions. Particular applications include lacquers, printing inks, leather dyes, wood stains, and various applications as a chemical intermediate or starting material for chemical syntheses.DEGEE belongs to the chemical class of glycol ethers which includes ethylene glycol ethers, diethylene glycol ethers, triethylene glycol ethers, and propylene glycol ethers. There are marked differences in the toxicity profile of these materials depending on the chain length of the alkoxy group and on the structure of the glycol group (ethylene glycol, diethylene glycol, or triethylene glycol). The short-chain (methyl, ethyl) ethylene glycol ethers cause testicular atrophy, embryotoxicity and teratogenic effects, and bone marrow suppression. The longer chain ethylene glycol ethers induce erythrocyte fragility in rats. Propylene glycol ethers have been shown to injure the liver and kidneys. 1 -Propylene glycol ethers have been reported as having teratogenic effects. The toxicological profiles of the glycol ethers have been reviewed by European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC, 1995).DEGEE is a member of the diethylene glycol ether group. The toxicity of this group of compounds is similar to that o...

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Atlas of Experimental Toxicological Pathology

Cited by 90 publications

References 0 publications

Optimization of an Animal Test Protocol for Toxicogenomics Studies (Ii); A Cross-Laboratory Gene Expression Analysis

Optimization of an Animal Test Protocol for Toxicogenomics Studies (Ii); A Cross-Laboratory Gene Expression Analysis

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

Twenty-Eight-Day Repeated-Dose Inhalation Exposure of Rats to Diethylene Glycol Monoethyl Ether

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