Correlations among human plasma levels of dioxin-like compounds and polychlorinated biphenyls (PCBs) and implications for epidemiologic studies.

In studies of the potential health effects of background-level exposure to organochlorine compounds (e.g., polychlorinated biphenyls, polychlorinated dibenzodioxins, and polychlorinated dibenzofurans), investigators have often measured either polychlorinated biphenyls or polychlorinated dibenzodioxins/polychlorinated dibenzofuransbut not both. We measured polychlorinated biphenyls (including specific non-, mono-, and di-ortho congeners) and specific polychlorinated dibenzodioxins/dibenzofurans among 63 Canadian blood donors. Levels of these compounds were, in general, fairly correlated. For example, Pearson's correlation coefficient between log total polychlorinated biphenyl and log total polychlorinated dibenzodioxins was .52. These results suggest that in epidemiologic studies of health effects of background-level exposures to these compounds, the quantitative dose-response relation observed for a given compound (or class of compounds acting through a similar mechanism) may easily be miscalibrated or confounded.

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine.

Substantial environmental pollution has been alleged in Ukraine, but little information is available to allow an assessment of the possible impact on humans. To help remedy this lack of information, it was of interest to investigate whether certain polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or coplanar polychlorinated biphenyls (PCBs) were elevated in people from Ukraine. Samples of breast milk were obtained from 200 women from the cities of Kyiv and Dniprodzerzhinsk; Kyiv is the capital and Dniprodzerzhinsk is a highly industrialized city. The samples were combined into four pools by city and age, and analyzed for 7 PCDDs, 10 PCDFs, and 2 coplanar PCBs (126 and 169). The total of the measured PCDDs, expressed as toxic equivalent, ranged from 5.1 to 7.6 pg/g lipid; for PCDFs from 3.6 to 5.2, and for PCBs from 11 to 18 pg/g lipid. Results from the two cities were similar; older women had slightly higher concentrations than did younger women. Levels of these compounds seen in Ukraine were similar to or lower than those seen in other recent studies from European and Asian countries.

Correlations among polychlorinated biphenyls, dioxins, and furans in humans.

BACKGROUND: Correlations among human levels of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans potentially complicate interpretation of studies of their individual health effects. Outcomes attributed to one may, in fact, be due to another. METHODS: We present correlations among dioxins, furans, and PCBs in blood collected in 1991-1992 from 44 American Vietnam veterans from Michigan. RESULTS: Correlations among specific dioxins and furans ranged from 0.26 to 0.80, with the higher-chlorinated congeners being more highly correlated. Correlations among PCBs ranged from 0.06 to 0.94, with those occurring at highest concentrations being more highly correlated. Correlations of PCBs with dioxins and furans ranged from -0.09 to 0.59. Correlations of individual chemicals with total dioxin toxic equivalents ranged from 0.31 to 0.76. DISCUSSION/CONCLUSIONS: If confirmed in other populations, such correlations may allow the use of simpler assays but may also raise issues of confounding and calibration.

Pesticide application and increased dioxin body burden in male and female agricultural workers in China.

Large amounts of the powerful pesticide sodium pentachlorophenol (Na-PCP) salt have been sprayed over vast areas in central China to control schistosomiasis, a parasitic disease of epidemic proportions. Approximately 6000 tons of Na-PCP are produced in China annually. Dioxins, a class of toxic, persistent compounds, are found as impurities in commercial Na-PCP products. These contaminants are released into the environment and significantly contribute to human exposure to dioxins in China. This study was carried out to determine dioxin levels in environmental and human tissue samples from one schistosomiasis area to evaluate the health risks associated with exposure to Na-PCP. Na-PCP pesticide was applied in 1972, 1973, and again in 1978. A total of approximately 454 tons and 902 tons of 5-ppm Na-PCP in water were sprayed over large land and lake problem schistosomiasis areas, respectively. The groups studied were (1) sprayers or handlers of Na-PCP, (2) persons living in the sprayed areas, and (3) persons living in unsprayed areas 300 km north of the sprayed lake located in a city in the Jiangxi province. Individual whole-blood and breast-milk samples were collected and later pooled for dioxin analysis. Also, a sample of commercial Na-PCP was collected. In addition, sediment samples from the lake where Na-PCP was sprayed were collected from four different sites and one control sample was collected from a non-schistosomiasis area. All of the samples were analyzed by high-resolution gas chromatography/mass spectrometry. A sample of Na-PCP used in schistosomiasis regions was analyzed and levels of 2,3,7,8-substituted dibenzodioxin (PCDD) and dibenzofuran (PCDF) congeners were measured. In addition, the international dioxin toxic equivalent (I-TEQ) value of this sample was calculated. Total I-TEQ of 162 parts per billion (ppb) was found in the Chinese Na-PCP product. A pooled breast-milk sample from mothers, female agricultural workers who were born in the schistosomiasis areas where large amounts of Na-PCP were sprayed, had an I-TEQ of 5,4 parts per trillion (ppt), lipid, which was about double that of mothers from control regions, women born in areas not sprayed with Na-PCP (2.6 ppt, lipid). The dioxin I-TEQ values in human blood ranged from 9.0 (subjects 15 to 19 years of age) to 16.3 ppt, lipid (subjects 35 to 70 years of age) in the whole-blood samples from Na-PCP exposed persons, whereas the general population's whole-blood I-TEQs were 4.8 and 6.4 ppt, lipid, respectively. The PCDD/F congener distribution patterns in four sediment samples from schistosomiasis areas were similar to that of Na-PCP. By comparison of specific "fingerprint" congeners (higher chlorinated dioxins and the closely related dibenzofurans) in Na-PCP, human tissues, and sediment samples, we conclude that the chemical pesticide Na-PCP is a source of environmental and human dioxin exposure in the Chinese schistosomiasis area studied. Although human PCDD/F tissue levels in China are low compared with those in more industrialized countries, the elevated I-TEQ levels in exposed persons are cause for concern.

Exposure of laboratory animals to polychlorinated dibenzodioxins and polychlorinated dibenzofurans from commerical rodent chow.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs) are ubiquitous low level environmental contaminants. Present finding of PCDDs and PCDFs in the human food supply suggested that laboratory animals maintained under controlled conditions may also receive unwanted exposure to these compounds from food. In this study, a commercial rodent chow, Prolab-RMH 1000, was analyzed for the toxicologically active 2,3,7,8-substituted PCDDs and PCDFs. The results show that the feed had a total PCDD/F dioxin toxic equivalence (I-TEq) of 0.13 pg/kg (ppt) wet weight. OCDD was the most abundant congener present, followed by 1,2,3,4,6,7,8-HpCDD, with these congeners representing the 5th and 6th greatest contributors to the calculated TEq. Daily ingestion of I-TEqs for the rats is calculated to be 3.9-6.5 pg/kg/day, and 13.0-32.5 pg/kg/day for mice. It is therefore important to consider the potential for background exposure to PCDDs and PCDFs from the diet when conducting studies with laboratory animals. This is particularly important when sensitive responses, such as enzyme induction, immunotoxicity, and developmental/reproductive toxicity are being investigated at very low exposures to this class of compounds.

Methadone use in patients with chronic renal disease.

Methadone disposition was studied in three patients receiving chronic methadone treatment and having chronic renal disease: one oliguric patient during peritoneal dialysis, one anuric patient on hemodialysis, and one patient following renal transplantation. In all three patients plasma levels of methadone remained within the desired therapeutic range (0.09--0.68 microgram/ml) for the doses received (40-50 mg/day). Elimination of methadone and its metabolites was almost exclusively by the fecal route in the anuric patient. Less than 1% of the daily dose was removed by peritoneal dialysis or hemodialysis. There was no laboratory or clinical evidence for accumulation of either methadone or its metabolites, suggesting that methadone is an appropriate narcotic to use in patients with renal disease.

A multidisciplinary clerkship in emergency medicine.

An obligatory, multidisciplinary, fourth-year emergency medicine clerkship is described and the particular problems of multidisciplinary courses discussed. The course is designed to produce medical students who adequately demonstrate: knowledge of emergency care and facility in specified skills, familiarity with the appropriate use of an emergency room, and conversance with treatment of nonemergency cases. Students are required to complete successfully an advanced cardiac life support providers course, serve on ambulance duty, rotate through a community hospital emergency room, and participate in the more traditional clinical experiences. The course offers the fourth-year student an opportunity to synthesize prior knowledge within the context of a multidisciplinary patient care experience.