No abstract

The accumulation of the plasticizer di-2-ethylhexylphthalate (DEHP) in blood and blood components has been of considerable concern for some time. We have followed the accumulation of DEHP and one of its major metabolities, mono-2-ethylhexylphthalate (MEHP) during storage of whole blood, platelet-rich plasma, platelet concentrates, and platelet-poor plasma for periods ranging from 72 hours to four weeks. Both phthalates showed a progressive increase in concentration with time. While the levels of DEHP were much greater than those of MEHP, there was nonetheless a significant and continual increase in MEHP in all preparations. The highest concentrations of both DEHP and MEHP were found in the platelet-poor plasma, indicating that platelets do not have a major role in the accumulation of the phthalates in blood. The accumulation of MEHP was shown to be a direct result of the metabolism of DEHP by plasma protein(s) rather than leaching from the blood bag.

These studies were undertaken to derive a lowest-observed-adverse-effect level (LOAEL) in the New Zealand White rabbit following a 91-day exposure to uranium (U, as uranyl nitrate hexahydrate, UN) in drinking water. Males were exposed for 91 days to UN in their drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L). Subsequently, females were similarly exposed for 91 days (4.8, 24, or 600 mg UN/L). Control groups were given tap water (< 0.001 mg U/L). Regular observations were recorded, and urine was collected periodically. Four males showed evidence of Pasteurella multocida infection and were excluded from the study. Following the study, all animals were euthanized, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and histopathological examination was performed. The hematological and biochemical parameters were not affected in a significant exposure-related manner. Dose-dependent differences consisted of histopathological changes limited primarily to kidney. Changes in renal tubules were characteristic of uranium toxicity. Based on changes in the tubular nuclei, the 91-day LOAEL for males in this study is 0.96 mg UN/L drinking water. The females drank 65% more water than the males, yet appeared to be less affected by the exposure regimen, although they also developed significant tubular nuclear changes in their lowest exposure group, deriving a LOAEL of 4.8 mg UN/L. Tissue uranium residue studies suggested that pharmacokinetic parameters for the males and females differ, possibly accounting for the difference in observed sensitivity to UN. An adverse effect of P. multocida infection cannot be excluded.

No abstract

These studies were undertaken to derive a lowest-observed-adverse-effect level (LOAEL) in the New Zealand White rabbit following a 91-day exposure to uranium (U, as uranyl nitrate hexahydrate, UN) in drinking water. Males were exposed for 91 days to UN in their drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L). Subsequently, females were similarly exposed for 91 days (4.8, 24, or 600 mg UN/L). Control groups were given tap water (< 0.001 mg U/L). Regular observations were recorded, and urine was collected periodically. Four males showed evidence of Pasteurella multocida infection and were excluded from the study. Following the study, all animals were euthanized, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and histopathological examination was performed. The hematological and biochemical parameters were not affected in a significant exposure-related manner. Dose-dependent differences consisted of histopathological changes limited primarily to kidney. Changes in renal tubules were characteristic of uranium toxicity. Based on changes in the tubular nuclei, the 91-day LOAEL for males in this study is 0.96 mg UN/L drinking water. The females drank 65% more water than the males, yet appeared to be less affected by the exposure regimen, although they also developed significant tubular nuclear changes in their lowest exposure group, deriving a LOAEL of 4.8 mg UN/L. Tissue uranium residue studies suggested that pharmacokinetic parameters for the males and females differ, possibly accounting for the difference in observed sensitivity to UN. An adverse effect of P. multocida infection cannot be excluded.