Histopathology limitations

In a chronic oral study in rats, observation of squinting and red discharge from the eyes were reported more frequently in trichloroethylene exposed rats as the study progressed (NCI 1976). Histopathological changes in the eyes were not reported in rats following chronic inhalation exposure (Maltoni et al. 1988) or in rats or mice following chronic oral exposure (Maltoni et al. 1986 NCI 1976 NTP 1988). Based on the limited data. 

Acute-Duration Exposure. Acute oral LD50 data are available for mice and rats (Hart 1976) and for ducks (Aulerich et al. 1979). Acute oral toxicity studies, including histopathological observations, are available for ducks, mice, rats, dogs, and mink (Aulerich et al. 1979 Hardisty et al. 1977 Hart 1976, 1980). Limited acute dermal toxicity are available for rats (Hart 1976). These data suggest a relatively low toxicity. However, a clear relationship between dose and effect has not been elucidated. Inhalation data of any kind were not identified, and dermal data were very limited. 

Mineral Oil Hydraulic Fluids. No studies regarding hepatic effects in humans following inhalation, oral, or dermal exposure to mineral oil hydraulic fluids were located. In an animal study, histopathological examination of the livers from rats exposed by inhalation to <1.0 mg/m3 of the water-in-oil emulsion hydraulic fluid Houghto-Safe 5047F for 90 days, 23 hours/day, showed no treatment-related lesions (Kinkead et al. 1991). Animal data for oral exposure are limited to one study where rats were exposed to MIL-H-5606 at 1,000 mg/kg/day for 26 days (Mattie et al. 1993). Increases in liver weight and peroxisomal beta-oxidation activity were observed. 

There has been no comprehensive evaluation of neurological function in animals after oral exposure to hexachloroethane. The data are limited primarily to clinical signs immediately after exposure and to histopathological evaluations of the brain tissues, which showed no effects. The highest NOAEL values and all LOAEL values from each reliable study for neurological effects in each species and duration category are recorded in Table 2-2 and Figure 2-2. 

Immunotoxicity. No studies are available for any exposure route on the potential for hexachloroethane to cause immunotoxic effects in humans. Data in animals are limited to studies that evaluated lymphoid organs (e.g., spleen and thymus) as part of a comprehensive histopathological examination following oral and inhalation exposure to hexachloroethane (Gorzinski et al. 1985 Weeks et al. 1979). Adverse effects were not reported for these organs. 

Information on immunological/lymphoreticular effects in test animals is limited to histopathological examination of tissues after intermediate-duration inhalation exposure to -hexane. No treatment-related lesions were observed in the cervical, bronchial, or mesenteric lymph nodes, thymus, bone marrow (sternum), or spleen of male Sprague-Dawley rats exposed to 500 ppm -hexane 22 hours a day for 6 months (IRDC 1981) or in mandibular and mesenteric lymph nodes, thymus, bone marrow, or spleen of Fischer 344 rats of both sexes exposed to up to 10,000 ppm for 6 hours a day, 5 days a week for 13 weeks (Cavender et al. 1984). Similar results were observed in mesenteric lymph nodes, thymus, bone marrow (sternum), and spleen in B6C3Fj mice exposed to -hexane at concentrations up to 10,000 ppm for 6 hours a day, 5 days a week for 13 weeks or 1,000 ppm for 22 hours a day, 5 days a week for 13 weeks (Dunnick et al. 1989 NTP 1991). 

Hepatic Effects. Workers monitored for liver function had increased serum levels of liver enzymes (Hoogendam et al. 1965). Only limited conclusions should be drawn from these results as the levels returned to normal within 1 week to 3 months concurrent exposure to other chemicals and alcohol was not controlled. Diffuse degenerative hepatic lesions were observed in rabbits and mice exposed to lethal doses of endrin and in surviving animals (Treon et al. 1955). Rats, mice, guinea pigs, and hamsters administered a relatively high dose of endrin exhibited moderate hepatic histopathology (Hassan et al. 1991). 

Mild diarrhea has also been observed in a 33-day gavage study in mice exposed to 10 mg/kg/day chlordecone. However, no effects on stomach or intestines at necropsy (Fujimori et al. 1983). Likewise, routine histopathological analyses of gastrointestinal tissues (described simply as "gut") also showed no compound-related effects in rats after 2 years of exposure at 1.25 mg/kg/day or in dogs after 124--128 weeks of exposure at 0.625 mg/kg/day (Larson et al. 1979b). Both of these studies are limited in that it is unclear whether tissues from all exposed animals were examined and the number of dogs used was too low (two/sex/dose). 

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