Focal necrosis

Mouse 2-12 Hepati c 5.2 (focal necrosis, cellular Huber 1965... 

Rat (albino) 5d Ix/d (G) Hepatic BdWt Other 770 M 770M (loss of appetite) 770 M (porphyria degeneration of hepatocytes focal necrosis) Rimington and Ziegler 1963... 

Other intermediate-duration oral studies with 1,4-dichlorobenzene have reported liver toxicity. In female rats dosed with 1,4-dichlorobenzene by gavage for about 6 months, doses of 188 mg/kg/day and above resulted in increased liver weights. At 376 mg/kg/day, slight cirrhosis and focal necrosis of the liver were also observed (Hollingsworth et al. 1956). No effects on the liver were seen at a dose of 18.8 mg/kg/day. Based on a minimal LOAEL (increased liver weight) of 188 mg/kg/day, an intermediate-duration MRL of 0.4 mg/kg/day was calculated as described in the footnote to Table 2-2 and Appendix A (Hollingsworth et al. 1956). 

Contact with skin may cause chemical burns. Conjunctivitis and focal necrosis of the cornea have been reported from eye exposure." ... 

After a single exposure of rabbits to 17 ppm for 6 hours, the sensory trigeminal nucleus was severely affected. Other effects included tubular and focal necrosis in the collecting tubules of the kidney and fatty degeneration of the liver. ... 

The LCso in mice for 60 minutes was 150 ppm effects were irritation of the eyes and nose and the delayed onset of labored breathing and lethargy autopsy findings included marked pulmonary congestion and hemorrhage. Mice exposed to sublethal concentrations had pulmonary irritation and delayed development of focal necrosis in the liver and kidneys. ... 

Oronasal exposure of mice to 2.6ppm led to a 50% decrease in respiratory rate. Mice exposed at 0.3, 1.0, and 2.6ppm 6 hour/day for 4, 9, and 14 days had lesions of the respiratory epithelium including squamous metaplasia, focal necrosis, and keratin exudate that were dose dependent at the lower exposure levels. Lesions persisted 2 weeks after exposure but were decreasing 4 weeks after the end of exposure. No exposure-related lesions were observed in the lungs of exposed mice. 

Oral doses of 2.5 ml of a 1 1 v/v mixture in olive oil were fatal to rats. A historical study indicates that exposure of rats to 800-900 ppm for 7 hours/day for six exposures caused hemorrhagic liver necrosis in some of the rats as well as focal necrosis of the kidneys. No deaths occurred from these exposures. 

Rabbits died from exposure to 10,000 ppm for 6 hours initial effects were weakness, ataxia, and muscular incoordination followed by convulsions. " The same concentration for 3 hours was not fatal. Autopsy of animals exposed to lethal concentrations showed focal necrosis in the liver and moderate kidney damage. Lower concentrations produced slight irritation of the respiratory tract, followed by mild narcosis, weakness, and salivation, but no evidence of eye irritation. 

In one acute-duration (24-hour) oral study in rats, hexachlorobutadiene caused focal necrosis of the kidneys and increased urinary biochemical parameters at doses of 100 mg/kg (Jonker et al. 1993a). Another acute-duration (14 days) oral exposure study revealed that hexachlorobutadiene caused renal tubular epithelial degeneration in rats at dose levels of 4.6 mg/kg/day or greater but no effects were seen in the liver up to doses of 35 mg/kg/day (Harleman and Seinen 1979). The number of animals in both of these studies were small and, thus, the data were not suitable for derivation of an MRL. 

Effects on the liver were observed in rats treated dermally (lateral abdominal area) with daily doses of 60 mg nickel/kg/day as nickel sulfate for 15 or 30 days (Mathur et al. 1977). The effects included swollen hepatocytes and feathery degeneration after 15 days and focal necrosis and vacuolization after 30 days. In this study, there was no indication that the rats were prevented from licking the nickel from the skin therefore, these effects could have resulted from oral... 

Little is known about the effects of 2,3-benzofuran exposure on humans. The principal adverse health effects noted in animals associated with oral exposure to 2,3-benzofuran are kidney and liver damage (NTP 1989). In the kidney, 2,3-benzofuran causes injury to the tubular cells, with degeneration, necrosis, and mineralization. In the liver, damage due to 2,3-benzofuran is usually characterized by focal necrosis of hepatocytes. However, the mechanism(s) associated with this damage are unknown. A better understanding of the mechanism of action of 2,3-benzofuran may make it possible to develop effective methods to reduce toxic effects caused by exposure. 

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