NOAEL and LOAEL determinations of acute hepatotoxicity for chloroform and bromodichloromethane delivered in an aqueous vehicle to F344 rats.

Chloroform (CHCl3) and bromodichloromethane (BDCM) are generally the two most prevalent disinfection by-products formed during chlorination of drinking water, and both have been shown to be hepatotoxic, nephrotoxic, and carcinogenic in rodents. As the toxicity of these trihalomethanes (THMs) has most often been studied with corn oil as the vehicle of administration, the objectives of this study were to assess hepatotoxicity after exposure to single, low dosages of CHCl3 and BDCM given orally in an aqueous vehicle to estimate a lowest-observed-adverse-effect level (LOAEL) and a no-observed-adverse-effect level (NOAEL) and to compare toxic potency. Ninety-day-old male Fischer 344 rats were gavaged with either 0.125, 0.1875, 0.25, 0.5, 0.75, 1.0, or 1.5 mmol CHCl3 or BDCM/kg body weight in 10% Alkamuls EL-620 (5 ml/kg body weight). At 24 h postgavage, serum was collected for analysis of clinical chemistry indicators of liver damage. Both CHCl3 and BDCM induced dose-dependent hepatotoxicity; serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase were elevated significantly over control at 1.5, 1.0, and 0.5 mmol/kg. At these dose levels after 24 h, the two THMs appeared to be equipotent hepatotoxicants. Additional assessments at later time points demonstrated that BDCM causes more persistent liver damage than CHCl3 (Lilly et al., 1997). At 0.25, 0. 1875, and 0. 125 mmol of either THM/kg, significant increases over control were not detected for any measured endpoint. Therefore, these data indicate that the acute, oral NOAELs and LOAELs for liver toxicity are 0.25 and 0.5 mmol/kg, respectively, for both CHCl3 and BDCM. These determinations should provide a basis to establish new exposure limits for One-Day Health Advisories for these prevalent THMs.

Improved post-transfusion quality of density separated AS-3 red cells after extended storage.

A centrifugal method of red cell density separation was utilized for unit processing in these studies to determine the quality of the lighter fraction (neocytes) after storage for up to 42 d and to evaluate whether the heavier fraction (gerocytes) deteriorated more rapidly than neocytes during storage. Each unit was passed through a Leukotrap filter to remove white cells prior to density separation. Red cell recovery and survival were evaluated using double label technetium-99m with either chromium-51 or nonradioisotopic chromium which permitted concurrent paired analysis. In vivo neocyte red cell recovery, as tested on the same 11 donors on days 1, 7 and 42 of storage, was effectively unchanged. Recovery and survival half-life (that is, the number of days after transfusion at which half of the cells infused remain in the circulation) of 42 d stored gerocytes were significantly lower than similarly stored neocytes (75.5 +/- 7.2% and 20.1 +/- 6.5 d for gerocytes versus 84.4 +/- 4.9% and 39.0 +/- 9.0 d for neocytes). One-day stored neocytes showed a 16.5% increase in red cell availability over the combined average for 42 d stored neocytes and gerocytes. Statistically, while there were significantly higher ATP, 2,3-DPG, and lactate levels pre-storage by paired t-test for neocytes compared to gerocytes, by day 42 there were no significant differences detected between the two red cell fractions by any of the in vitro variables measured. These studies suggest that this simple separation technique for leucocyte-poor red cell units provides a neocyte population with improved viability and the potential for increased transfusion intervals in chronically transfused patients.

Studies with nonradioisotopic sodium chromate. I. Development of a technique for measuring red cell volume.

A nonradioisotopic method for measuring red cell volume that involves the use of 52Cr-sodium chromate as the red cell label and of graphite furnace atomic absorption analysis of chromium is described. The technique allows the labelling of 20 mL of packed red cells with 40 to 50 micrograms of sodium chromate (Na2CrO4) in 30 minutes at 22 degrees C with 94 +/- 6 percent uptake. Approximately 40 micrograms of Na2CrO4 was injected for in vivo studies. This results in posttransfusion in vivo red cell chromium levels after sample processing in the range of 1 to 7 micrograms per L, which could be quantitated accurately (coefficient of variation = 4.7%) by Zeeman electrothermal atomic absorption spectrophotometry. The labeling concentration of chromium did not cause increased hemolysis, and the labeled cells exhibited an osmotic fragility curve similar to that of unlabeled, fresh ACD red cells. Red cell glutathione peroxidase was unaffected by labeling, although glutathione reductase was reduced by approximately 13 percent (p less than 0.05). The 52Cr red cell volume-measuring method was evaluated by concurrent in vivo studies with the standard 51Cr and 125I-albumin methods for that procedure. Simultaneous measurement of red cell volumes in seven volunteers by the 51Cr, 52Cr, and 125I-albumin techniques correlated highly with each other (r greater than 0.76), with mean values of 2294 +/- 199, 2191 +/- 180, and 2243 +/- 291 mL, respectively. The standard deviations of the differences were small: 134 mL for 52Cr versus 51Cr and 183 mL for 52Cr versus 125I.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic nephelometric determination of transthyretin and retinol-binding protein in neonatal serum.

We have developed a kinetic immunonephelometric method for the determination of retinol-binding protein and modified the method of Jacob et al (Clin Chem 1983; 29: 564) for the determination of transthyretin (prealbumin) in neonatal serum specimens from small, premature infants. The methodologies allow detection of 17.5 mg/l transthyretin and 1.7 mg/l retinol-binding protein in 25 microliter of serum. Between-run precision studies using pooled neonatal serum gave CV values of 3% and 5-6% for transthyretin and retinol-binding protein, respectively. Results obtained for neonatal specimens using this method agreed well with those obtained for the same specimens using radial immunodiffusion. Mean (SD) serum concentrations for 39 neonatal specimens were 100.4 (46.6) and 26.3 (10.8) mg/l for transthyretin and retinol-binding protein, respectively.