Hepatitis toxic

OCPs, different types of clinical deviations in the nervous system were observed asthenia (23.6%), asthenoautonomic syndrome (28.1%), and autonomic vascular disruptions (34.5%) almost 40% suffered from an enlarged liver, 33.8% from toxic hepatitis, and 84.2% from disruptions in kidney functions. 

Overall, it should not be surprising that damage to the liver (e.g. viral or toxic hepatitis) or genetic defects affecting pathways within the tissue often lead to pathology. 

Acute toxic hepatic effects of 1,2-dibromoethane consisting of hepatocellular cloudy swelling, centrilobular fatty change, and patchy necrosis were reported in animals after a single inhalation exposure (Rowe et al. 1952). Repeated inhalation exposures of rats and rabbits to 100 ppm... 

The MRL was based on a LOAEL of 14 ppm in workers exposed to concentrations of chloroform of up to 400 ppm for less than 6 months (Phoon et al. 1983). Vomiting and toxic hepatitis were noted to occur at an inhaled chloroform concentration of 14 ppm. The LOAEL of 14 ppm was divided by an uncertainty factor of 100 (10 for the use of a LOAEL and 10 for human variability) and a modifying factor of 3 (insufficient diagnostic data to determine the seriousness of hepatotoxic effects) to arrive at the MRL of 0.05 ppm. Alterations in liver functions have been reported in several studies in both humans and animals, and is discussed in more detail in the chronic-duration inhalation MRL section immediately below. 

Hepatic Effects. The liver is a primary target organ of chloroform toxicity in humans and animals after inhalation and oral exposure, with some evidence that suggests that the damage may be reversible (Wallace 1950). Impaired liver function was indicated by increased sulfobromophthalein retention in some patients exposed to chloroform via anesthesia (Smith et al. 1973). Acute toxic hepatitis developed after childbirth in several women exposed to chloroform via anesthesia (Lunt 1953 Royston 1924 Townsend 1939). 

An intermediate-duration oral MRL was derived based on liver effects in dogs (Heywood et al. 1979). An intermediate-duration inhalation MRL was derived based on toxic hepatitis which occurred in humans (Phoon et al. 1983). Pharmaeokinetie data regarding dermal exposure to chloroform are limited, but it is known that ehloroform can be absorbed through the skin. Intermediate-duration dermal studies in animals would provide information about ehloroform toxieity via this exposure route. The information would be... 

An MRL of 0.05 ppm has been derived for intermediate-duration inhalation exposure to ehloroform. The MRL is based on a LOAEL of 14 ppm for toxic hepatitis in workers exposed to up to 400 ppm for less than 6 months (Phoon et al. 1983). 

Hakim A, Jain AK, Jain R. 1992. Chloroform ingestion causing toxic hepatitis. J Assoc Physicians India 40(7) 477. 

Experimental design The study describes outbreaks of toxic hepatitis in workers occupationally exposed to chloroform in two different factories. Mostly women were employed in both places. 

Some studies of occupationally exposed groups have revealed evidence of liver injury by serum enzyme studies or other liver function tests. Adverse effect and dose-effect relationships have not been consistent within and between studies, raising the possibility that other factors (e.g., alcohol intake, other exposures) could be responsible. Review of these studies indicates that some liver effects may have occurred with repeated exposures at concentrations below O.lmg/m assuming RGBs were responsible. Several deaths due to toxic hepatitis have been reported among workers exposed to mixtures of RGBs with chlorinated naphthalenes such effects have not been observed with PGB exposure alone. ... 

Occupational exposure of 12 male workers, whose hands were in contact with MDA several hours per day, caused toxic hepatitis. The clinical pattern of the cases included right upper quadrant pain, high fever, and chills with subsequent jaundice. A skin rash was seen in five of the cases. Percutaneous absorption was considered to be the major route of exposure because workers in the same occupational setting who did not have direct skin contact with MDA were not affected. All patients recovered within 7 weeks, and follow-up more than 5 years later showed no biochemical or clinical evidence of chronic hepatic disease. 

McGill DB, Motto JD An industrial outbreak of toxic hepatitis due to methylenedi-aniline. N EnglJ Med 291 278-282, 1974... 

Two men accidentally exposed to DMN developed toxic hepatitis. There are no reports of chronic effects from human exposure. ... 

Industrial exposure to tricbloronaphthalene (usually mixed with tetrachloronaphtha-lene) has been relatively free of untoward effects compared witb tbe more bigbly chlorinated naphthalenes. No fatal cases of liver injury have been reported, but one instance of toxic hepatitis supposedly resulted from exposure to 3mg/m Altbougb there are several reports of chloracne from exposure to tricbloronaphthalene, they do not stand up well to critical analysis. Experiments on human volunteers showed that the mist was entirely nonacneigenic as opposed to the penta- and hexachloro derivatives, which produce severe chloracne. ... 

Deaths from aplastic anemia and toxic hepatitis were reported in TNT workers before the 1950s with improved industrial practices, there have been few reports of fatalities or serious health problems related to its use. ... 

Hepatic Toxicity Hepatic toxicity including hepatic failure resulting in transplantation or death has been reported. Severe and sometimes fatal hepatitis associated with disulfiram therapy may develop even after many months of therapy. Hepatic toxicity has occurred in patients with or without prior history of abnormal liver function. Advise patients to immediately notify their physician of any early symptoms of hepatitis (eg, fatigue, weakness, malaise, anorexia, nausea, vomiting, jaundice, dark urine). 

Hepatic Hepatic cholestasis, hepatic toxicity, hepatitis, hyperbilirubinemia, increased liver enzymes, jaundice, liver failure. 

Brent JA, Rumack BH. 1993. Role of free radicals in toxic hepatic injury II. Are free radicals the cause of toxin-induced liver injury Clin Toxicol 31 173-196. 

Clark, F., and D. R. Reed. Chaparral-induced toxic hepatitis. California and Texas, 1992. MMWR Morbid Mortal Wkly Rep 1992 41(43) 812-814. Anon. From the Food and Drug Administration. Public Warning about herbal product Chaparral . J Amer Med Ass 1993 269(3) 328. 

The uncommon allergic reactions include acute toxic hepatitis, toxic nephrosis and acute haemolytic anaemia. 

Grek O, Kolpakov M, Bashkirov Yu et al (2000) Use of Enterosgel for correction of disturbance of liver function in experimental chronic toxic hepatitis. In Clinical use of Enterosgel preparation in patients with pathology of organs of digestive system, Moscow (In Russian), pp 63-66... 

Some cases of hepatotoxicity have been reported to be associated with exposure to coumarin. One possible case was reported by Beinssen (1994) and six by Loprinzi et al. (1997). Marshall et al. (1994) reported one case in which elevated serum aminotransferase levels were measured in a patient given 5 g coumarin per day. In two lymphoedema patients given 90 mg coumarin per day for five months, Koch et al. (1997) reported elevated serum alanine aminotransferase activity. Faurschou (1982) reported a case of toxic hepatitis in a patient given coumarin daily for eight weeks, which was characterized by hepatomegaly and elevated serum enzyme levels. All signs of liver toxicity returned to normal on cessation of treatment. 

Evans, J.G, Appleby, E.C., Lake, B.G Coiming, D M. (1989) Studies on the induction of cholangiofibrosis by coumarin in the rat. Toxicology, 55, 207-224 Faurschou, P. (1982) Toxic hepatitis due to benzo-pyrone. Hum. Toxicol, 1, 149-150 Fentem, J.H. Fry, J.R. (1991) Comparison of the effects of inducers of cytochrome P450 on Mongolian gerbil and rat hepatic microsomal monooxygenase activities. Xenobiotica, 21, 895-904... 

Carboplatin Same as cisplatin Non-small cell and small cell lung cancer, breast cancer, bladder cancer, head and neck cancer, ovarian cancer Nausea and vomiting Myelosuppression rarely peripheral neuropathy, renal toxicity, hepatic dysfunction... 

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