Fatty metamorphosis

Rats exposed to 1000 ppm of vapors for 4—7 h/d for eight days showed ataxia, decreased body weight and growth rate, and minimal central fatty metamorphosis of the Hver (119). Trichloroethanol and trichloroacetic acid were urinary metaboHtes. Tetrachloroethylene did not show any of these effects. 

This MRL for mirex was derived using a NOAEL of 0.075 mg/kg/day for dose-dependent hepatic changes from a study by NTP (1990). The dose-dependent changes included increased fatty metamorphosis (cytoplasmic vacuoles consistent with intracellular fat accumulation) and necrosis of hepatocytes (focal and/or centrilobular) in F344/N rats of both sexes at a dose of 0.7 mg/kg/day... 

The EPA has derived an oral reference dose (RfD) of 2.00x10 Vig/kg/day for mirex (IRIS 1994). The RfD is based on liver cytomegaly, fatty metamorphosis, angiectasis, and thyroid toxicity in rats (NTP 1990). No reference concentration is available for mirex. Neither a reference dose nor a reference concentration exist for chlordecone. 

Hepatic Effects. No studies were located regarding hepatic effects of 1,2-diphenylhydrazine in Humans. Chronic oral administration of 1,2-diphenylhydrazine produced degenerative alterations the liver of rats (fatty metamorphosis) and mice (coagulative necrosis) (NCI 1978). 

After twelve months of feeding, two of the five rats fed browned egg albumin exhibited mild fatty metamorphosis. This was not detected in the control egg albumin group. Again, this fatty change was within a normal range. No significant lesions were detected in the instant breakfast or hydrolyzed egg albumin groups. 

Gn pig (NS) 35 wk 2 or 4x/wk (GO) Hepatic 0.75 (moderate to marked fibrosis, parenchymal fatty metamorphosis, slight bile duct proliferation, hypertrophy, atrophy) Ashburn et al. 1948... 

Benzene is metabolized primarily in the liver by the cytochrome P-450 system (Parke 1989). It appears that the metabolism of benzene by the hepatic cytochrome P-450 system plays an important role in its bioactivation and toxicity. Sammett et al. (1979) provided corroborative evidence of this by showing that partial hepatectomy of rats diminished both the rate of metabolism of benzene and its toxicity. An increase in altered hepatic foci has been shown in male rats after benzene exposure in conjunction with initiator and promotor administration (Dragan et al. 1993). A dose of 500 mg/kg of benzene administered subcutaneously once daily, 5 days a week for 26 weeks to Wistar rats resulted in focal fine droplet fatty metamorphosis with accompanying lymphoidal infiltration in the liver after 12 weeks (Bloch et al. 1990). In some cases a proliferated histocyte-like cells formed clusters in the vicinity of the periportal fields. After 26 weeks, more diffuse steatosis, feathery degeneration of hepatocytes, single necrotic cells were seen. 

Shaw GR, Anderson WR. Multisystem failure and hepatic microvesicular fatty metamorphosis associated with tolmetin ingestion. Arch Pathol Lab Med 1991 115(8) 818-21. 

The comparative toxicity of four symmetrical hexachlorobiphenyl isomers was studied in mice (Biocca et al. 1981). Male mice were fed several dose levels of PCB 136, PCB 153, PCB 155, andPCB 169 daily for 28 days. The hepatic LOAEL (foamy cells and microabscesses) was 200 pg/kg/day for PCB 169 and much higher for the other congeners at 21.4 mg/kg/day. Liver effects induced at doses higher than the LOAEL included fatty metamorphosis (PCBs 155 and 169) and increased liver porphyrins (PCB 169). 

Cardio Hepatic 8 8 (fatty metamorphosis, increased liver weight) ... 

In dogs orally administered 50,100,250,500,800, or 1200 mg/ kg methyl salicylate for up to 10 weeks, no adverse effects were noted in animals receiving 250 mg/kg or less, but an increasing dose-dependent fatty metamorphosis of the liver was observed at higher test levels (Webb and Hansen 1963). 

Among the advanced HCC tumors, the typical expansive type of HCC is a sharply demarcated lesion that may be unifocal or multifocal, lypical features of expansive type HCC include tumor capsule and internal mosaic architecture. Most expansive HCC lesions have a well-developed fibrous capsule. The fibrous capsule is demonstrated by CT as a hypoattenuating rim which enhances in the delayed phase (Karahan et al. 2003 Ros et al. 1990). Internal mosaic architecture is characterized by components separated by thin fibrous septa. The different components may show various attenuation indexes on CT images, particularly if areas of well-differentiated tumor with different degrees of fatty metamorphosis are present. Internal septa show delayed enhancement, similar to that of the fibrous capsule (Fig. 13.9) (Yoshikawa et al. 1992). The infiltrative type HCC is characterized by an irregular and indistinct tumor-nontumor boundary. This type is demonstrated as a mainly uneven hypodense area with unclear mar-... 

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