Acute mastoiditis in infants: penicillin-resistant Streptococcus pneumoniae and its therapy

Earlier studies in our laboratory showed that hydroxylated metabolites of polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) competitively inhibit thyroxine (T4) binding to transthyretin (TTR) and type I deiodinase (D1) activity. In this study, we investigated the possible inhibitory effects of hydroxylated metabolites of polyhalogenated aromatic hydrocarbons (PHAHs) on iodothyronine sulfotransferase activity. Rat liver cytosol was used as a source of sulfotransferase enzyme in an in vitro assay with 125I-labeled 3,3'-diiodothyronine (T2) as a model substrate. Increasing amounts of hydroxylated PCBs, PCDDs, or PCDFs or extracts from incubation mixtures of PHAHs and induced liver microsomes were added as potential inhibitors of T2 sulfotransferase activity. Hydroxylated metabolites of PCBs, PCDDs, and PCDFs were found to be potent inhibitors of T2 sulfotransferase activity in vitro with IC50 values in the low micromolar range (0.2-3.8 microM). The most potent inhibitor of T2 sulfotransferase activity in our experiments was the PCB metabolite 3-hydroxy-2,3',4, 4',5-pentachlorobiphenyl with an IC50 value of 0.2 microM. A hydroxyl group in the para or meta position appeared to be an important structural requirement for T2 sulfotransferase inhibition by PCB metabolites. Ortho hydroxy PCBs were much less potent, and none of the parent PHAHs was capable of inhibiting T2 sulfotransferase activity. In addition, the formation of T2 sulfotransferase-inhibiting metabolites of individual brominated diphenyl ethers and nitrofen as well as from some commercial PHAH mixtures (e.g., Bromkal, Clophen A50, and Aroclor 1254) was also demonstrated. These results indicate that hydroxylated PHAHs are potent inhibitors of thyroid hormone sulfation. Since thyroid hormone sulfation may play an important role in regulating free hormone levels in the fetus, and PCB metabolites are known to accumulate in fetal tissues after maternal exposure to PCBs, these observations may have implications for fetal thyroid hormone homeostasis and development.     

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.     

Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study

As a consequence of contamination by effluents from local electronics manufacturing facilities, the New Bedford Harbor and estuary in southeastern Massachusetts is among the sites in the United States that are considered the most highly contaminated by polychlorinated biphenyls (PCBs). Since 1993, measures of intrauterine PCB exposure have been obtained for a sample of New Bedford area infants. Among 122 mother-infant pairs, we identified four milk samples with total PCB levels that were significantly higher than the rest, with estimated total PCBs ranging from 1,100 to 2,400 ng/g milk fat compared with an overall mean of 320 ng/g milk fat for the 122 women. The congener profile and history of one case was consistent with past occupational PCB exposures. Otherwise, the source of PCB exposures in these cases was difficult to specify. Environmental exposures including those from fish consumption were likely, whereas residence adjacent to a PCB-contaminated site was considered an unlikely exposure source. In all four cases, the infants were full-term, healthy newborns. Because the developing nervous system is believed to be particularly susceptible to PCBs (for example, prenatal PCB exposures have been associated with prematurity, decrements in birth weight and gestation time, and behavioral and developmental deficits in later infancy and childhood, including decrements in IQ), it is critical to ascertain if breast-feeding is a health risk for the women's infants. Despite the potential for large postnatal PCB exposures via breast milk, there is limited evidence of significant developmental toxicity associated with the transmission of moderate PCB concentrations through breast milk. Breast-feeding is associated with substantial health benefits including better cognitive skills among breast-fed compared with formula-fed infants. We conclude, based on evidence from other studies, that the benefits of breast-feeding probably outweigh any risk from PCB exposures via breast milk among the four New Bedford infants. In this case report, PCB analysis of breast milk and infant cord serum was a research tool. PCB analysis of milk is rarely done clinically, in part because it is difficult to use the results of such analyses to predict health risks. Substantial effort is needed to achieve a better understanding of the clinical and public health significance of PCB exposures, particularly among potentially susceptible groups such as infants and children. Such efforts are critical to improving the clinical and public health management of widespread and ongoing population exposures to PCBs.     

Dioxin-like PCBs in the environment-human exposure and the significance of sources

Dioxin-like PCBs represent an important component of the Sigma-TEQ in many environmental media. Specifically, in animal produce and in fish PCBs dominate the Sigma-TEQ ingested by humans. This in turn leads to high background body burdens in humans with PCB-TEQ greater than that associated with PCDD/Fs. High fish consumers are apparently subject to elevated TEQ exposure from dioxin-like PCBs. This has important implications for exposure assessment studies which have previously only been concerned with PCDDs and PCDFs. Unlike PCDD/Fs, dioxin-like PCBs are not controlled within the food chain. Sources and pathways of exposure are poorly defined. Aroclor formulations and their subsequent usage are considered to be the most important sources in terms of human exposure to some TEF-rated congeners, notably PCB-118, PCB-156 and part of PCB-126. Emissions from combustion sources contribute additional PCB-126. More research is needed to place these compounds in an integrated risk evaluation framework.     

The toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and their relevance for toxicity

This article reviews the present state of the art regarding the toxicokinetics and metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). The absorption, body distribution, and metabolism can vary greatly between species and also may depend on the congener and dose. In biota, the 2,3,7,8-substituted PCDDs and PCDFs are almost exclusively retained in all tissue types, preferably liver and fat. This selective tissue retention and bioaccumulation are caused by a reduced rate of biotransformation and subsequent elimination of congeners with chlorine substitution at the 2,3,7, and 8 positions. 2,3,7,8-Substituted PCDDs and PCDFs also have the greatest toxic and biological activity and affinity for the cytosolic arylhydrocarbon (Ah)-receptor protein. The parent compound is the causal agent for Ah-receptor-mediated toxic and biological effects, with metabolism and subsequent elimination of 2,3,7,8- substituted congeners representing a detoxification process. Congener-specific affinity of PCDDs and PCDFs for the Ah-receptor, the genetic events following receptor binding, and toxicokinetics are factors that contribute to the relative in vivo potency of an individual PCDD or PCDF in a given species. Limited human data indicate that marked species differences exist in the toxicokinetics of these compounds. Thus, human risk assessment for PCDDs and PCDFs needs to consider species-, congener-, and dose-specific toxicokinetic data. In addition, exposure to complex mixtures, including PCBs, has the potential to alter the toxicokinetics of individual compounds. These alterations in toxicokinetics may be involved in some of the nonadditive toxic or biological effects that are observed after exposure to mixtures of PCDDs or PCDFs with PCBs.     

Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants

Effects of postnatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs) on thyroid hormone status were studied in the peripheral blood of 36 breast-fed Japanese infants. Estimated total intakes of these chemicals in toxic equivalent quantity (TEQ) converted into 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) from the breast milk significantly and negatively correlated with the levels of triiodothyronine (T3) and thyroxine (T4) in the blood of breast-fed babies. Therefore, exposure to background levels of the highly toxic organochlorine chemicals through the breast milk may cause some effects on thyroid hormone status in Japanese infants.     

A comparison of dioxins, dibenzofurans and coplanar PCBs in uncooked and broiled ground beef, catfish and bacon

The primary source of dioxins (PCDDs), dibenzofurans (PCDFs) and coplanar PCBs for the general population is food, especially meat, fish, and dairy products. However, most data on the levels of these chemicals is from food in the raw or uncooked state. We report here the effect of one type of cooking (broiling) on the levels of PCDDs, PCDFs, and coplanar PCBs in ground beef (hamburger), bacon and catfish. Samples of hamburger, bacon, and catfish were broiled and compared to uncooked samples in order to measure changes in the amounts of dioxins in cooked food. The total amount of PCDD, PCDF, and coplanar PCB TEQ decreased by approximately 50% on average for each portion as a result of broiling the hamburger, bacon and catfish specimens. The mean concentration (pg TEQ/kg, wet weight) of PCDDs, PCDFs, and coplanar PCBs, however, remained the same in the hamburger, increased by 83% in the bacon, and decreased by 34% in the catfish. On average, the total measured concentration (pg/kg) of the congeners of PCDDs, PCDFs, and coplanar PCBs increased 14% in the hamburger, increased 29% in the bacon, and decreased 33% in the catfish.     

Estimated intake of PCDDs, PCDFs and co-planar PCBs in individuals from Madrid (Spain) eating an average diet

The estimated intake of PCDD/Fs and co-planar PCBs associated with an average diet consumed in Spain was investigated. The estimated total average intake for PCDDs and PCDFs from an average spanish diet was found to be 142 pg I-TEQ/day (2.4 pg I-TEQ/Kg b.w./day, for a 60 Kg person). PCDDs provided almost 80% of the total dioxin equivalents. This represents the upper bound estimate. If concentrations less than the LOD are taken as equal to zero, then the estimated average intake would be 81 pg I-TEQ/day which is the lower bound estimate. Data reported are in good agreement with those reported for other countries.     

Polychlorinated diphenyl ethers, dibenzo-p-dioxins, dibenzofurans and biphenyls in seals and sediment from the Gulf of Finland

Polychlorinated diphenyl ethers (PCDEs), 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in seals from the Gulf of Finland and in sediments from the Gulf of Finland and near Gotland. The sediments included one surface core from both sampling sites. The seal material consisted of 14 ringed seals and 6 grey seals that all were found dead and examined for pathology. The main aims were to scrutinize levels and patterns of PCDEs for the first time in seals from the Baltic Sea and to estimate whether chlorinated compounds mentioned have an influence on an exceptional high mortality that occurred among ringed seals in the Gulf of Finland in late 1991. The concentrations of 50 congeners of tetra- through deca-CDEs analyzed ranged from < 0.3 to 62 ng/g lipid weight (lw) in seal blubber, but in the sediments PCDEs were non-detectable (tetra- through hepta-CDEs < 0.1 ng/g dry weight (dw)). In ringed seals with good nutritional status, the concentrations of almost all PCDE congeners were greater in two adult females than in specimens of younger age groups. The concentrations of PCDDs and PCDFs as TCDD-equivalents exceeded those of the coplanar (non-ortho) PCBs in sediments, whereas non- and monoortho PCBs constituted greater toxic loads as those calculated for PCDDs and PCDFs in seals. However, the levels revealed do not explain the high mortality of ringed seals.     

Polychlorinated dioxin and dibenzofuran levels in the environment and food from the Republic of Bashkortostan, Russia

The paper summarises systematic 5-year monitoring of the environment, drinking water and food for PCDDs and PCDFs levels in industrial centres and in rural areas of the Republic of Bashkortostan, Russia. It also presents selected data on dioxin concentrations in gas emissions of toxic waste incinerators at chemical plants. The paper gives a comparative analysis of PCDDs/PCDFs daily intake by the population of industrial cities for Bashkortostan and for industrial countries of Europe and North America. The results show that PCDDs/PCDFs levels in the environment, drinking water and food in Bashkortostan are approximately equal to those in other industrial countries.     

Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake

Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, "dioxin") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.     

Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer--results from a case-control study

Organochlorines are persistent and highly lipophilic environmental contaminants which bioaccumulate in the food chain. Some of these chemicals, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), have been suggested to be of significance in the aetiology of breast cancer. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an anti-oestrogen in animal studies and should be thus lower the risk of breast cancer. The other isomers of polychlorinated dibenzo-p-dioxins (PCDDs) or the chemically related polychlorinated dibenzofurans (PCDFs) have not been tested regarding carcinogenesis of the breast. The purpose of this study was to investigate whether PCDDs or PCDFs influence the risk for breast cancer. Consecutive patients who underwent surgery for a breast disease between 1993 and 1995 were recruited for the study. Cases were 22 patients with infiltrative breast cancer and controls were 19 patients operated for a benign breast disease during the same time period. Approximately 10 g of breast tissue free from tumour was taken from the specimen and frozen until analysis. Fat was extracted, cleaned and analysed with a high-resolution gas chromatograph coupled to a high-resolution mass spectrometer. Median concentrations of octachlorinated dibenzo-p-dioxin (OCDD) were 598 (170-14,880) and 396 (103-1,847) pg/g lipid in the cases and in the controls, respectively. In a multivariate logistic regression analysis controlling for other risk factors for breast cancer increased odds ratio (OR) was obtained for OCDD: 401-1000 pg/g lipid yielded OR 3.8, 95% confidence interval (CI) 0.4-39, > 1000 pg/g lipid gave OR 5.2, CI 0.4-72. When the lipid OCDD variable was examined as a continuous risk factor there was a 1.09 (9%), CI 0.95-1.25, increase in the adjusted OR for breast cancer per 100 unit (pg/g lipid) increase in OCDD. No differences were found between cases and controls for the other six tested PCDDs. Mean concentration of TCDD was in the cases 3.6 (1.0-7.9) and in the controls 3.3 (1.1-6.3) pg/g lipid. For PCDFs no significant differences were found between cases and controls. The results were not changed if oestrogen or progesterone receptor status, S-phase fraction and DNA ploidy were considered. Breast tissue concentration of OCDD was increased in cancer patients, whereas the concentrations of other PCDDs and PCDFs were equal in cases and controls.     

Interactions between 2,3,7,8-TCDD and PCBs as tumor promoters: limitations of TEFs

The assessment of the carcinogenic risk of polychlorinated dioxins (PCDDs), furans (PCDFs), and biphenyls (PCBs) by TEFs is hampered by species- and tissue-specific responses that cannot readily be explained by differences in the Ah receptor levels but may be due to events subsequent to ligand binding to the Ah receptor. Moreover, PCDDs and related compounds accumulate in the environment, in animal and human tissues as highly complex mixtures. Thus, comprehensive risk assessment should include all Ah receptor ligands and agents that modulate the Ah receptor-mediated responses. Tumor promoter studies with mixtures of PCDDs and halogenated biphenyls have shown additive, synergistic, and antagonistic effects. To analyse the interactions of TCDD and PCBs as tumor promoters in more detail, we established an in vitro assay, i.e., the enhancement (promotion) of malignant transformation of carcinogen-initiated C3H/M2 mouse fibroblasts after treatment with tumor promoters. The coplanar PCB 126, a potent Ah receptor agonist, and the diortho-substituted PCB153, to which no TEF value has been ascribed, are promoters of malignant transformation. A defined mixture of PCB126 and TCDD had an additive promoting effect, while PCB 153 antagonized the TCDD-mediated promotion. Thus, the TEF-approach may be insufficient to estimate the tumor-promoting activities of PCDDs, PCDFs, and PCBs in mammalian tissues in which diortho-substituted PCBs are greatly accumulated.     

Symposium overview: the use of delayed matching-to-sample procedures in studies of short-term memory in animals and humans

The authors examined the hypothesized association between the body burden of polychlorinated biphenyls (PCB) in women and the risk of low birth weight for their infants. In Sweden, a main exposure route for PCBs and other persistent organochlorine compounds is through the consumption of fatty fish from the Baltic Sea (on the Swedish east coast). A previous comparison between a cohort of consumers of large quantities of fish from the Swedish east coast and a reference population, together with a following analysis based on questionnaire data from a case-control study within the east coast cohort, supported the hypothesized association. In 1995, blood samples were collected from the wives and ex-wives of fishermen from the Swedish east coast (n = 192) who had given birth during the period 1973-1991. Cases (n = 57), i.e., infants with low birth weight (1,500-2,750 g), were matched with controls (n = 135; birth weight, 3,250-4,500 g) on gender, parity, and calendar year of birth. The concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed; it has been suggested that CB-153 is a relevant biomarker of exposure to PCBs. The concentration of CB-153 in the plasma of mothers during the year of childbirth was "estimated" using some alternative plausible kinetic models. For two alternative estimated exposure datasets, which were focused on separately, an increase in the risk of a low birth weight was observed at a CB-153 concentration of 300 and 400 ng/g lipid weight, respectively (adjusted odds ratios of 2.1 (95% confidence interval (CI) 1.0-4.7) and 2.3 (95% CI 0.9-5.9)). The present results strengthen the findings reported previously for this study population.     

Effect of postnatal exposure to a PCB mixture in monkeys on multiple fixed interval-fixed ratio performance

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microgram(s)/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). At 4 years of age, performance under a multiple fixed interval (FI)-fixed ratio (FR) schedule of reinforcement was assessed. The FI component was more sensitive to disruption as a result of PCB exposure than was the FR component. PCB-exposed monkeys displayed shorter mean interresponse times (IRTs) than controls, particularly during the earlier sessions of the experiment. Similarly, the increase in pause time characteristic of the acquisition of typical FI performance emerged more slowly across sessions in the PCB-treated group. However, the number of short IRTs (less than 5 s) remained greater in the treated group compared to controls over the 48-session duration of the experiment. On the FR component, control monkeys decreases the mean pause time across sessions whereas the PCB-treated group did not; there were no differences between groups for absolute value of average IRT or pause time. The results of this study extend previous research in this cohort of monkeys, and provide further evidence that PCB exposure limited to the early postnatal period and resulting in environmentally relevant body burdens produces long-term behavioral effects.     

Breast-feeding exposure of infants to cadmium, lead, and mercury: a public health viewpoint

The purpose of this report is to provide an overview of the public health implications of exposure via breast milk to cadmium, lead, and mercury for nursing infants and to provide health-based guidance. Daily intakes were calculated and compared with guidance values used for public health assessments at hazardous waste sites. Cadmium, lead, and mercury under normal conditions are found in breast milk at concentration ranges of < 1 microgram/L, 2-5 micrograms/L, and 1.4-1.7 micrograms/L, respectively. Women exposed environmentally or occupationally can have higher levels in their breast milk. Concentrations of about 5 micrograms/L (cadmium), 20 micrograms/L (lead), and 3.5 micrograms/L (mercury) appear to be adequate screening levels. Many factors affect both the distribution of cadmium, lead, and mercury in breast milk and the health consequences to an infant. It is not clear what additional impact low-level exposure via breast milk may have on an infant born with a body burden to one of these metals. There is sufficient evidence to make the case that contaminated breast milk is a source of potential risk to infants in certain populations. Prevention strategies that include behavior modification and proper nutrition should be communicated to women at risk. Identification and elimination of exposure pathways and a critical analysis of the benefits of breast feeding versus heavy metal exposure are needed on a site-specific or individual basis. Research is required to better understand the impact of low-level exposure to heavy metals via breast milk. Breastfeeding should be encouraged under most circumstances.     

Lack of suppressive effects of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFS), and aroclor biphenyls (PCBS) on mixed lymphocyte reaction, phagocytic, and natural killer cell activities of rat leukocytes in vitro

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to determine the immunotoxicity of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs). The mixtures were based on the concentrations of the chemicals in fish flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1-2 microg/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 microg/ml), or combinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immunological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cultured with mitomycin C-treated Long-Evans splenocytes by [3H]thymidine uptake. Exposure to MeHg (2 microg/ml) alone or with PCB/ PCDD/PCDF resulted in significant cytolethality in rat splenocytes, peritoneal leukocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixtures, PCDD/PCDF mixtures, 0.1 microg MeHg/ml (noncytolethal), or PCB/PCDD/PCDF mixtures with 0.1 microg MeHg/ml caused no suppression of splenocyte MLR response, splenic NK cell-mediated lysis of Yac-l cells, or phagocytosis of fluorescent beads by splenic, peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects on the immune functions assayed, and thus produced no additive immunotoxicity. However, in order to predict the potential risk of these chemical mixtures to the human immune system, in vivo animal studies with blood (tissue) levels compatible with the levels of MeHg, PCBs, and PCDDs/PCDFs in exposed human populations should be evaluated.     

Primary fallopian tube cancer: a review of the literature

BACKGROUND: We conducted a population-based case-control study to describe the relationship between occupational exposure to estrogenic chemicals and the occurrence of breast cancer in Cape Cod, Massachusetts. METHODS: Incident cases of breast cancer (n = 261) diagnosed from 1983 through 1986 and controls (n = 753) were interviewed to gather information on breast cancer risk factors and all full-time jobs held since age 18. Blinded exposure assessments were employed using the data from the NIOSH National Occupational Exposure Survey, chemical production and usage information, and the expert judgement of a certified industrial hygienist. RESULTS: Overall, 29.5% of cases and 32.5% of controls had probable occupational exposure to one or more xenoestrogens. Probable exposure to nonylphenol (21.5% of cases, 21.4% of controls), butyl benzyl phthalate (10.0% of cases, 13.2% of controls), BHA (7.3% of cases, 9.6% of controls), bisphenol A (9.6% of cases, 11.6% of controls), and 4-tert-butylphenol (2.7% of cases and 5.3% of controls) were relatively commons, while probable exposure to the other xenestrogens was rare. Only PCBs and 4-octylphenol were associated with moderate increase in the odds of breast cancer (PCBs: 5 exposed cases and 6 exposed controls, adjust odds ratio: 3.2, 95% CI = 0.8-12.2, and 4-octylphenol: 6 exposed cases and 5 exposed controls, adjusted odds ratio: 2.9, 95% CI = 10.8).     

Decreased response to phototherapy for neonatal jaundice in breast-fed infants

OBJECTIVE: To evaluate the efficacy of phototherapy for nonhemolytic hyperbilirubinemia in breast-fed and formula-fed infants and infants receiving formula and breast milk. DESIGN: Prospective study. SETTING: Nursery for healthy infants. METHOD: Full-term healthy infants with nonhemolytic hyperbilirubinemia (bilirubin concentration, >255 micromol/L [14.9 mg/dL] or 222 micromol/L [13.0 mg/dL] at ages younger than 48 hours) were treated with conventional phototherapy by using daylight fluorescent lamps. Three groups of infants were studied: group 1, formula-fed infants; group 2, breast-fed infants; and group 3, infants receiving formula and breast milk. All patterns of feeding started at birth. Phototherapy was terminated only when bilirubin concentrations had decreased to less than 185 micromol/L (10.8 mg/dL); the minimum exposure period was 24 hours. RESULTS: A total of 163 infants were studied: group 1, 79; group 2, 34; and group 3, 50. The age at the start of exposure was comparable in all groups. The mean+/-SD weight loss as a percentage of birth weight was as follows: group 1, 2.8%+/-5.0%; group 2, 6.1%+/-3.4%; and group 3, 3.2%+/-2.6%. The duration of exposure to phototherapy was as follows: group 1, 54.1+/-20.8 hours; group 2, 64.6+/-25.1 hours; and group 3, 54.9+/-21.5 hours; the 24-hour rate of decrease in the bilirubin concentration was as follows: group 1, 18.6%+/-11.7%; group 2, 17.1%+/-9.6%; and group 3, 22.9%+/-9.4%. The overall rate of decrease in the bilirubin concentration for the duration of exposure to phototherapy was as follows: group 1, 0.8%+/-0.3% per hour; group 2, 0.6%+/-0.3% per hour; and group 3, 0.8%+/-0.3% per hour. Weight loss at the start of phototherapy was significantly greater in group 2 compared with group 1 (P<.001) and group 3 (P<.001), although the hemoglobin and hematocrit values were comparable. The duration of exposure to phototherapy was not significantly different in the 3 groups (P=.06); however, the duration of exposure of group 2 infants was 10 hours more than that of the other 2 groups. The 24-hour rate of decrease in the bilirubin concentration in group 3 was significantly better than that of group 2 (P = .007) and group 3 (P = .02); the rates of decrease for groups 2 and 3 were similar (P = .52). The overall rate of decrease in the bilirubin concentration during the duration of exposure to phototherapy in group 2 was significantly less than that of group 1 (P = .002) and group 3 (P<.001); the rates for groups 1 and 3 were similar (P = .35). The postexposure rebound bilirubin concentrations were comparable in all groups during the first 2 days; however, the duration of moderate jaundice in group 2 was more prolonged. CONCLUSIONS: The response to phototherapy of group 2 infants was significantly slower than that of group 3 and group 1 infants; this response was still of adequate efficacy. The addition of formula to the feedings for totally breast-fed infants, without suspension of breast-feeding, would enhance the efficacy of phototherapy and reduce exposure time.     

Levels of dioxins, dibenzofurans, PCB and DDE congeners in pooled food samples collected in 1995 at supermarkets across the United States

Food, particularly dairy products, meat, and fish, has been identified as the primary immediate source of intake of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) for the general population. We previously reported PCDD/Fs in individual analyses of food samples from a number of countries, including the U.S., the former Soviet Union, and Vietnam. We also previously estimated daily intake of dioxins and related chemicals in Americans at various ages in these reports. In this paper, the levels of dioxins, dibenzofurans, dioxin toxic equivalents (TEQs), selected dioxin-like PCBs, and DDE (a persistent metabolite of DDT) were measured in 12 pooled food samples from over 90 individual specimens collected from supermarkets throughout the United States during 1995. Samples were pooled by food groups and then analyzed. Food samples were collected in Binghamton, New York; Atlanta, Georgia; Chicago, Illinois; San Diego, California; and Louisville, Kentucky. In addition to the meat, dairy, and fish samples, a vegan (all vegetable, fruit and grain, no animal product) diet, was simulated; this showed the lowest level of dioxins.