Liver human case studies

Based on a combination of available human case studies and experiments with laboratory animals, the major public health concerns associated with exposure to 1,4-dichlorobenzene are effects on the liver, kidneys, and blood. Some immunological, dermatological, and neurological effects have also been reported in exposed humans. There is information from animal studies which raises the question of whether 1,4-dichlorobenzene can cross the placenta and elicit structural effects on the developing fetus. Data from a study conducted in rats using the intraperitoneal route have demonstrated sperm abnormalities. Cancer of the liver as a result of lifetime exposure to 1,4-dichlorobenzene has been shown in mice, and renal cancer has been reported in male rats. However, recent studies related to the mechanism of renal carcinogenesis in rats suggest that these tumors may not be expected to occur in exposed humans. Issues relevant to children are explicitly discussed in Section 2.6, Children s Susceptibility, and Section 5.6, Exposures of Children. 

Samples of stomach contents, blood, bile, adipose tissue, liver, brain, and kidney were collected at autopsy of a woman who ingested a lethal dose estimated at 293 mg/kg of a diazinon formulation ("FERTI-LOME" bagworm spray) containing 10% diazinon (Poklis et al. 1980). The highest concentrations were found in the blood, followed by stomach contents and the bile. Lowest concentrations were found in the kidney, followed by adipose tissue, and then bile. Animal studies confirmed the human case study in that diazinon is widely distributed in all analyzed tissues in rats (Miicke et al. 1970), in sheep (Janes et al. 1973 Machin et al. 1971, 1974), and in cows (Abdelsalam and Ford 1986). 

A successful case study for asymmetric nitrogen oxidation was reported for a series of (hetero)aromatic tertiary amines. High diastereoselectivity was observed for the enzyme-mediated oxidation of S-(—)-nicotine by isolated CHMOAdneto to give the corresponding ds-N-oxide [215]. The stereoselectivity of this biooxidation was complementary to the product obtained by flavin M O (FM O) from human li ver (trows-selective [216]) as well as unspecific oxidations by FMOs from porcine and guinea pig liver. 

Case Study 1 An evaluation of the human relevance of the synthetic pyrethroid metofluthrin-induced liver tumors in rats based on mode of action [115-117]... 

Only one report of human death attributed to 1,4-dichlorobenzene exposure has been located in the literature. A 60-year-old man and his wife died within months of each other due to acute yellow atrophy of the liver (also known as massive hepatic necrosis or fulminant hepatitis) (Cotter 1953). Their home had been "saturated" with 1,4-dichlorobenzene mothball vapor for a period of about 3-4 months, but no air measurements were available. Clinical symptoms included severe headache, diarrhea, numbness, clumsiness, slurred speech, weight loss (50 pounds in 3 months in the case of the husband), and jaundice. The wife died within a year of the initial exposure however, it was not clear if 1,4-dichlorobenzene was the primary cause of death. This case study did not address whether these individuals consumed excessive amounts of alcohol or had previous medical problems, such as a chronic liver infection. 

Death. There are some data to suggest that lethality may be a public health concern for persons exposed for prolonged periods of time to high levels of 1,4-dichlorobenzene in confined areas (e.g., in homes). The only available information related to the death of humans exposed to 1,4-dichlorobenzene is a case study of a 60-year-old man and his wife who both died of liver ailments after the air in their home had been found to contain increased air concentrations of 1,4-dichlorobenzene (described as saturated ) for 3-4 months (Cotter 1953). However, the exact air concentration of 1,4-dichlorobenzene was not measured or reported, nor was the existence or nature of other possible factors contributing to their deaths (e.g., pattern of alcohol consumption, exposure to other chemicals, or pre-existing medical... 

Hepatic Effects. Liver effects reported in case studies in humans exposed to 1,4-dichlorobenzene via inhalation have included jaundice, cirrhosis, and atrophy (Cotter 1953). Estimates of exposure duration ranged from 1 to 18 months however, quantitative data on 1,4-dichlorobenzene levels were not available. One report was located that described a 3-year-old boy who may have ingested 1,4-dichlorobenzene crystals. Jaundice was reported, indicating that liver function was in some way compromised, although no further details were reported. No dermal exposures to 1,4-dichlorobenzene in humans were reported. The lack of reliable information regarding human exposures to 1,4-dichlorobenzene by all three routes of exposure makes it difficult to draw any helpful conclusions about the toxicity of 1,4-dichlorobenzene in humans. 

Death. The only reports, of death in humans are case studies of two workers who died of liver failure 3 or 5 years after exposure to tetryl dust in a manufacturing plant (Hardy and Maloof 1950). 

Strohmeyer, F.W., Ishak, K.G. Nodular transformation (nodular regenerative hyperplasia) of the liver A clinicopathologic study of 30 cases. Human Pathol 1981 12 60-71... 

Death. Occupational exposure of humans to 2,4-DNP has resulted in death (Gisclard and Woodward 1946 Perkins 1919). This exposure included airborne vapor, mists, dust, and direct dermal contact with the solid form of 2,4-DNP, indicating that exposure probably occurred via inhalation, dermal, and possibly oral routes. Death from occupational exposure to 2,4-DNP appeared to occur at a greater rate in workers having alcoholism or liver or kidney disease (Perkins 1919). Case studies reported death in humans ingesting 2,4-DNP and its sodium salt (doses expressed here as mg/kg... 

Hepatic Effects. Although there were no indications of liver effects in studies of controlled human exposure to 1,1,1-trichloroethane, data from case reports of overexposed humans suggest that this chemical may produce mild hepatic effects in humans exposed to high levels. 

Pastoor, T., Rose, P., Lloyd, S., Peffer, R., and Green, T. (2005). Case study Weight of evidence evaluation of the human health relevance of thiamethoxam-related mouse liver tumors. Toxicol Sci 86, 56-60. 

Liver biopsy specimens from eight cases, and autopsy material from one human case and two dogs were studied. Characteristic features were centrizonal scarring, hepatic venous occlusion, ductular proliferation and cholestasis, focal S mcytial giant-cell transformation of hepatocytes, and pericellular fibrosis. 

CHRONIC HEALTH RISKS (note there are no well-documented studies showing the effects of terphenyls on humans) Cases of dermatitis attributed to skin contact with terphenyls have been reported may cause liver and kidney damage, as based on testing in animals. 

In the first case study, a lead candidate 12 (Fig. 6) was assessed for its potential to form reactive metabolites in LC-MS-based trapping assays using a variety of trapping agents. There were no indications of the formation of any thiol or cyanide adducts when GSH, N-acetylcysteine, or cyanide were included in incubations of 12 with human liver microsomes. However, when a tritium-labeled derivative of 12 was incubated with human liver microsomes under standard conditions... 

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