benzofurans and 1-2-3-4-7-8-hexachlorodibenzofuran

The concentrations of immunoglobulins (IgA, IgD, IgG, IgM) and of several cytokines were measured in the plasma of volunteers with clearly, but moderately, increased body burdens of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), using monoclonal antibodies and an enzyme-linked immuno-sorbant assay. Two groups of workers with different body burdens of PCDD/PCDF were studied: (trial I) persons with mainly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and (trial II) persons with mainly penta- and hexachlorinated dibenzofurans (P5CDF/H6CDF) in their blood fat. Including the reference group, 158 volunteers were investigated. A slight but statistically significant decrease was observed in the plasma concentration of IgG1 in persons exposed to TCDD, but not in persons exposed to P5CDF/H6CDF. When the data of both groups were pooled and a multi-regression analysis against international TCDD toxicity equivalencies (I-TEq, NATO/CCMS) was performed, taking several confounding factors into account, no influence of the dioxin exposure could be revealed. There were no changes in the plasma concentrations of the other immunoglobulins studied. In the same volunteers, no deviation from the reference range was found for the concentrations of the cytokines: IL-1alpha, IL-1beta, IL-6 and TNFalpha in blood plasma.

Topics: Adult; Aged; Benzofurans; Body Burden; Cytokines; Female; Humans; Immune System; Immunoglobulin G; Male; Middle Aged; Occupational Exposure; Polychlorinated Dibenzodioxins; Receptors, Cell Surface

Children secondarily exposed through their mothers to a toxic rice oil containing PCDFs and PCBs in the Yu-cheng incident have shown developmental delay even a decade after the incident. Forty-five serum samples were collected from these children in February 1991 ad small amounts analyzed for their contaminant content using sample enrichment and isotope dilution mass spectrometry. In about one-half the samples, detectable levels of PCDFs and PCBs could still be determined with average values for 2, 3, 4, 7, 8-PnCDF and 1, 2, 3, 4, 7, 8-HxCDF of 300 and 620 ng/kg serum lipid, respectively. The mean of the total PCBs on a whole weight basis was 7.5 micrograms/kg. These concentrations of PCDFs and PCBs are still 10 to 25 times higher than those from a matched control population. Although the serum levels did not correlate with developmental delays, those for the two PCDFs but not the total PCBs correlated with duration of breast feeding indicative of postnatal exposure. The results of this study suggest that estimation of past prenatal exposure of children to PCDFs is best carried out using current mother and not current child blood concentrations.

Topics: Adult; Benzofurans; Child; Cohort Studies; Female; Food Contamination; Gas Chromatography-Mass Spectrometry; Humans; Oryza; Plant Oils; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects

Previous studies showed that 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) could produce tumors in the liver and subcutaneous tissues of rats by subcutaneous administration. The present study has examined the carcinogenicity of the same compounds in rats by oral administration. Wistar strain male rats were sacrificed at two years after oral administration (0.2 mg/rat) of 2,3,4,7,8-PenCDF or 1,2,3,4,7,8-HCDF. Among rats given 2,3,4,7,8-PenCDF, a cholangiohepatoma and a osteosarcoma were revealed in a rat each. Moreover, a few hepatic nodules were found in two rats in each experimental group. These results suggest that these compounds of polychlorinated dibenzofurans have a tumorigenic potency by oral administration.

Topics: Administration, Oral; Animals; Benzofurans; Male; Neoplasms, Experimental; Rats; Rats, Inbred Strains

2,3,7,8-Tetrachlorodibenzo-p-dixoin 2,3,4,7,8-pentachlorodibenzofuran (PCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) are highly toxic members of a class of environmental contaminants, the polychlorinated aromatic hydrocarbons (PCAH), which exhibit a similar and highly characteristic spectrum of toxic effects. For purposes of risk assessment, it is important to be able to make accurate estimates of the relative potency of these and related compounds. Previous investigations have indicated that, in acute exposure or in vitro studies, PCDF is approximately 0.1 times as toxic and HCDF is approximately 0.01 times as toxic as TCDD. In this study, we compared the relative toxicity and tumor-promoting abilities of TCDD, PCDF, and HCDF in hairless mouse skin. Female hairless mice (HRS/J hr/hr) were treated dermally with the initiator MNNG, then dosed twice weekly for 20 weeks with acetone, TCDD (2.5-10 ng/mouse/dose), PCDF (25-100 ng/mouse/dose), or HCDF (250-1000 ng/mouse/dose) as promoter. TCDD, PCDF, and HCDF were all potent promoters for the induction of squamous cell papillomas. There was, however, no difference in the incidence or multiplicity of papilloma formation between groups. The same doses of the three PCAH, in the absence of initiator, induced no skin papillomas. TCDD produced a significant increase in liver:body weight ratio (p less than 0.001) at all doses and a decrease in thymus:body weight ratio at a dose of 10 ng (p less than 0.001). Mice treated with PCDF and HCDF had marked thymic and splenic involution, liver hypertrophy, mucous cell hyperplasia in the fundic portion of the glandular stomach, and loss of body weight. PCDF and HCDF produced a greater incidence and severity of dermatotoxic effects than TCDD. Based on data for dermal toxicity and changes in body weight and organ weights, PCDF is estimated to be 0.2 to 0.4 times, and HCDF 0.08 to 0.16 times, as toxic as TCDD following repeated dermal exposure. Therefore, toxic equivalence factors generated using data from acute and/or in vitro studies may underestimate the risk from repeated low-dose exposures to these compounds.

Topics: Animals; Benzofurans; Carcinoma, Squamous Cell; Dioxins; Female; Hypertrophy; Liver; Mice; Mice, Hairless; Papilloma; Polychlorinated Dibenzodioxins; Skin; Skin Diseases; Skin Neoplasms

2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) are environmental contaminants which mimic many of the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Like TCDD, these polychlorinated dibenzofurans (PCDFs) induce hepatic benzo[a]pyrene hydroxylase activity (BPH) and possess high affinity for the Ah receptor. Another similarity of these PCDFs to TCDD is their ability to induce teratogenic effects such as cleft palate and hydronephrosis in mice. Recent studies have shown that TCDD modifies the equilibrium binding kinetics of the rat liver cytosolic glucocorticoid receptor (GRc) and the hepatic plasma membrane epidermal growth factor (EGF) receptor. To gain a better understanding of the action of halogenated hydrocarbons on these cytosolic and membrane-bound receptor systems during pregnancy, we investigated the biochemical effects of PeCDF and HCDF on the binding kinetics of maternal mouse liver GRc and EGF receptors and the induction of BPH activities. Pregnant C57BL/6N mice were treated once daily on gestation Days 10 through 13 with PeCDF (0-30 micrograms/kg) or HCDF (0-300 micrograms/kg). Hepatic [3H]dexamethasone and [125I]EGF equilibrium binding studies indicated that all doses of PeCDF tested (10, 20, and 30 micrograms/kg) significantly reduced the GRc and EGF receptor maximum binding capacities but did not affect the binding affinities of these receptors when compared to corn oil-treated control pregnant mice. Similar effects were observed for doses of HCDF greater than or equal to 100 micrograms/kg. These data suggest that the dibenzofuran-mediated decreases in GRc and EGF receptor binding capacities are similar to those caused by TCDD. Although the mechanism of action is not yet clear, our results indicate that halogenated aromatic compounds in addition to TCDD have profound effects on both steroid and growth factor receptor systems.

Topics: Animals; Benzofurans; Dose-Response Relationship, Drug; ErbB Receptors; Female; Liver; Mice; Mice, Inbred C57BL; Polychlorinated Dibenzodioxins; Pregnancy; Receptors, Glucocorticoid

Two isomers of polychlorinated dibenzofurans, 2,3,4,7,8-pentachlorodibenzofuran or 1,2,3,4,7,8-hexachlorodibenzofuran, both of which are present in the yusho patients, were subcutaneously administered to rats in a single non-lethal dose to examine acute or subacute toxicity. Maximal inhibition of increase in body weight and decrease in daily locomotor activity were observed in the rats treated with 370 micrograms/kg of these compounds at 3 to 4 weeks after treatment, especially with 2,3,4,7,8-pentachlorodibenzofuran. Histopathologically, hypertrophy of the liver and atrophy of the thymus were noted at 4 weeks after treatment with this dose, while bile duct hyperplasia in the liver was observed at 40 weeks after treatment with 250 micrograms/kg of these compounds.

Topics: Animals; Benzofurans; Body Weight; Dose-Response Relationship, Drug; Liver; Male; Motor Activity; Rats; Rats, Inbred Strains; Time Factors

In order to examine the carcinogenicity of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran, these two chemicals were subcutaneously administered to Wistar strain male rats at the dose of 80 micrograms, 40 micrograms or 4 micrograms per rat. At sacrifice in two years after the start of the experiment, tumors were observed in the subcutaneous tissue and the liver. Although the number of the rats used is small, the tumor occurrence showed some tendency to relate with the dose of the chemicals given.

Topics: Animals; Benzofurans; Fibroma; Fibrosarcoma; Lipoma; Liver Neoplasms, Experimental; Male; Rats; Rats, Inbred Strains; Skin Neoplasms

Enhancement of diethylnitrosamine(DENA)-induced hepatic tumor production in rats was observed by sequential exposure to 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) or 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF). This effect was more evident in the group of rats treated with 2,3,4,7,8-PenCDF (80 micrograms/rat), in which approximately 43% of this compound administered was accumulated in the liver at 8 weeks after the last treatment.

Topics: Animals; Benzofurans; Body Weight; Diethylnitrosamine; Liver Neoplasms, Experimental; Male; Polymers; Rats; Rats, Inbred Strains; Thymus Gland