Hepatic hyperplasia

Reversible diffuse mild swelling of hepatocytes, decreased SGPT activity, increased liver weight in dogs mild hepatic hyperplasia, increased hepatocyte vacuolization in rats fatty changes in hepatocytes, increased hepatocytic vacuolization, increased liver adenomas in mice... 

Hepatic effects such as elevated liver enzyme levels, nodular hepatic hyperplasia, fatty changes, necrosis, fibrosis, and bile duct proliferation were observed in rats and dogs following chronic exposure to MBOCA (Stula et al. 1975, 1977). Chronic exposures to high levels of MBOCA at hazardous waste sites may induce similar adverse hepatic effects. 

Chuang, S.E., Cheng, A.L., Lin, J.K., and Kuo, M.L., Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats, Foorf Client. Toxicol, 38 (11) 991-995,2000. 

Hepatic peroxisome proliferation, characterized by liver enlargement due to hyperplasia and hypertrophy, has been proposed as a basis for differences in species susceptibility to trichloroethylene carcinogenicity. Peroxisomes are membrane-bound organelles which contain enzymes generally involved in lipid metabolism. 

Hepatic Renal 350 200 (diffuse hyperplasia of bladder epithelium)... 

Chronic animal studies of organophosphates are few in number, but those that do exist provide a useful base from which to draw toxicological insight. In rats and mice exposed orally to tricresyl phosphate for 2 years, endocrine effects were found in a dose-response pattern and hepatic effects were found. Ovarian interstitial hyperplasia was also observed but was not dose related. No chronic-duration MRLs could be derived because of the limited number of studies. Tricresyl phosphate, a component of certain hydraulic fluids, produced no evidence of carcinogenic activity in assays with rats and mice (NTP 1994). However, another component, tributyl phosphate, was associated with an increased incidence of bladder tumors in rats and mice (FMC 1994a, 1994b). 

Dose-related incidence of hepatic nodular hyperplasias in the 25 and 50 mg/kg diets and an increased incidence of hepatomas in the male 5- and 25-mg/kg groups. Controls experienced a high incidence of premature deaths (Epstein 1976)... 

A wide spectrum of hepatic lesions has been reported in AIDS (H4), but it is not known whether the changes are related to the presence of HIV-1. Therefore, sections from livers of autopsied patients with AIDS were examined for the presence of HIV-1 antigen p 24 (core) and gp 41 (envelope) by the avidin-biotin-peroxidase complex methods using monoclonal antibodies. The most common histologic abnormalities were steatosis, portal inflammation, Kupffer cell hyperplasia, and focal hepatocellular and bile duct damage. Immunoreactivity for HIV-1 antigens was demonstrated in 80% of cases. 

Several studies have reported hepatic effects in animals after exposure to HMX. Hepatocyte hyperplasia and cytoplasmic eosinophilia were noted in rats and mice orally exposed to 1280 and 300mg/kg/day, respectively, for 14 days. Clear evidence of hepato-toxicity was observed at a higher dose of 8504mg HMX/kg/day, which resulted in cen-trilobular degeneration in male rats exposed for 14 days. Collectively, the data from animal studies indicate that the liver is adversely affected by exposure to moderate to high doses of HMX. 

Rats exposed to 207 ppm daily for 6 months developed hepatic neoplasms hepatocellular hyperplasia and necrosis occurred after 3 months of exposure at this concentration. In another series of inhalation experiments on rats, 200 ppm produced hepatocellular carcinomas in both sexes 100 ppm resulted in liver tumors in males after 12 months of exposure... 

Hepatic and splenic lesions were observed after subchronic oral studies in rodents. Rats exposed to 2300mg/kg/day in the diet for 7 weeks experienced a moderate to marked increase in splenic hematopoiesis. A high incidence of bone marrow hyperplasia and leukocytosis occurred in rats after chronic exposure to about 1300mg/kg/day in the diet. 

Hepatic lesions (adenomas, focal nodular hyperplasia, hepatocellular carcinoma, etc) Rarely, benign and malignant hepatic adenomas have been associated with the use of hormonal contraceptives. Severe abdominal pain, shock, or death may be due to rupture and hemorrhage of a liver tumor. 

Adverse reactions may include the following Fever porphyria dysuria gout hepatic reaction nausea vomiting anorexia thrombocytopenia and sideroblastic anemia with erythroid hyperplasia vacuolation of erythrocytes increased serum iron concentration adverse effects on blood clotting mechanisms mild arthralgia and myalgia hypersensitivity reactions including rashes, urticaria, pruritus fever acne photosensitivity porphyria dysuria interstitial nephritis. 

Male Insomnia, chills, decreased libido, hepatic dysfunction, nausea, diarrhea, prostatic hyperplasia (elderly), iron deficiency anemia, suppression of clotting factors... 

Kombrast, D.J., Barfknecht, T.R. Ingram, P. (1984) Effect of di(2-ethylhexyl)phthalate on DNA repair and lipid peroxidation in rat hepatocytes and on metabolic cooperation in Chinese hamster V-79 cells. J. Toxicol, environ. Health, 13, 99-116 Kurata, Y., Kidachi, F., Yokoyama, M., Toyota, N., Tsuchitani, M. Katoh, M. (1998) Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol. Sci., 42, 49-56... 

Most of the synthetic androgens and anabolic agents are 17-alkyl-substituted steroids. Administration of drugs with this structure is often associated with evidence of hepatic dysfunction. Hepatic dysfunction usually occurs early in the course of treatment, and the degree is proportionate to the dose. Bilirubin levels may increase until clinical jaundice is apparent. The cholestatic jaundice is reversible upon cessation of therapy, and permanent changes do not occur. In older males, prostatic hyperplasia may develop, causing urinary retention. 

Thyroid effects that have mainly included reduced serum T4 hormone levels and follicular cell hyperplasia were consistently observed in rats and mice orally exposed to PBDEs. Accompanying changes in serum TSH levels were not found and the depression of serum T4 is likely related to hepatic enzyme induction. Acute duration studies showed decreases in serum T4 in rats exposed to >10 mg/kg/day octaBDE or >30 mg/kg/day pentaBDE for 4 days and in rats and mice exposed to >18 mg/kg/day pentaBDE for 14 days. Effects observed in intermediate-duration studies include thyroid hyperplasia in rats exposed to >8 mg/kg/day octaBDE for 30 days and reduced serum T4 in rats exposed to >10 mg/kg/day pentaBDE for 90 days. Exposure to pentaBDE on gestation day 6 through postnatal day 21 caused serum T4... 

---