Postmortem changes in the pH of blood and selected tissues in rats were evaluated at intervals ranging from 2 min to 96 h. Cardiac blood pH was significantly and reproducibly decreased in all groups at all postmortem intervals, independent of the method of sacrifice used. A preliminary study using cardiac blood obtained at autopsy from a limited number (n = 11) of human subjects demonstrated a significant negative correlation (r = −0.908, P < 0.01) between postmortem interval (range 2 to 20 h) and cardiac blood pH.
1,3-Propanediol was a specialty chemical that, due to a novel manufacturing process, is now commercially available in large quantities. Its subchronic toxicity has been evaluated in rats, with special emphasis on potential male reproductive effects. 1,3-Propanediol in deionized water was administered orally by gavage to three groups of 10 male and 10 female Crl:CD(SD)BR rats for a period of 90 consecutive days. Dosage levels were 100, 300, and 1000 mg/kg/day, and a control group received water at a constant volume of 10 ml/kg/day. All animals survived to the scheduled necropsy, and there were no effects on the clinical condition of the animals, body weights, body weight gains, food consumption or organ weights. There were no effects on hematology or serum chemistry parameters. Spermatogenic endpoints were unaffected in all treated males. No treatment-related changes were observed on macroscopic or microscopic examinations of selected organs. Under the conditions of the study, the no-observed-effect level (NOEL) for systemic toxicity of 1,3-propanediol administered orally via gavage to male and female rats for 90 consecutive days was 1000 mg/kg/day, the highest dose tested.
Simultaneous administration of trichloroethylene (TCE), at an oral dose of 0.5 mVkg, resulted in a marked potentiation of liver injury caused by an oral dose of carbon tetrachloride (CCl,, 0.05 mVkg). Hepatic glutathione levels were depressed at 24 hr only in the rats given TCE and CCl,. Using serum enzyme (ALT and SDH) as indicators of hepatotoxicity, potentiation of CCl,-injury was most apparent at 24 hr. Upon histological examination of H&E stained liver sections, the differences between livers obtained from TCE and CC1,-treated rats versus CC1,-treated rats were most apparent at later time points (48 and 72 hr). At 48 hr after CCl,, livers showed a distinctive and uniform pattern of injury with regeneration features predominating over necrosis. At this time, livers from TCE and CC1,-treated rats were characterized by extensive zone 3 coagulative necrosis. Inflammatory infiltrations were less prominent. At 72 hr, morphological features of livers from TCE and CCl, rats were similar to those from ralSgven CCl, alone at 48 hr. From the results obtained, it appears that the regenerative activity of the liver may be delayed in rats simultaneously administered TCE and CCI, as compared to rats administered only CCI,.
Fischer-Tropsch (FT) Synthetic Paraffinic Kerosene (SPK) jet fuel is a synthetic organic mixture intended to augment petroleum-derived JP-8 jet fuel use by the U.S. armed forces. The FT SPK testing program goal was to develop a comparative toxicity database with petroleum-derived jet fuels that may be used to calculate an occupational exposure limit (OEL). Toxicity investigations included the dermal irritation test (FT vs. JP-8 vs. 50:50 blend), 2 in vitro genotoxicity tests, acute inhalation study, short-term (2-week) inhalation range finder study with measurement of bone marrow micronuclei, 90-day inhalation toxicity, and sensory irritation assay. Dermal irritation was slight to moderate. All genotoxicity studies were negative. An acute inhalation study with F344 rats exposed at 2000 mg/m for 4 hr resulted in no abnormal clinical observations. Based on a 2-week range-finder, F344 rats were exposed for 6 hr per day, 5 days per week, for 90 days to an aerosol-vapor mixture of FT SPK jet fuel (0, 200, 700 or 2000 mg/m). Effects on the nasal cavities were minimal (700 mg/m) to mild (2000 mg/m); only high exposure produced multifocal inflammatory cell infiltration in rat lungs (both genders). The RD (50% respiratory rate depression) value for the sensory irritation assay, calculated to be 10,939 mg/m indicated the FT SPK fuel is less irritating than JP-8. Based upon the proposed use as a 50:50 blend with JP-8, a FT SPK jet fuel OEL is recommended at 200 mg/m vapor and 5 mg/m aerosol, in concurrence with the current JP-8 OEL.
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