Differential accumulation of low-chlorinated (Delor 103) and high-chlorinated (Delor 106) biphenyls in human placental tissue and opposite effects on conversion of DHEA to E2.

OBJECTIVE: Polychlorinated biphenyls (PCBs) and related compounds elicit a diverse spectrum of toxic responses. Additionally, they are able to pass through the human placenta. The aim of the presented data was to compare the action of low-chlorinated (Delor 103) and (Delor 106) high-chlorinated biphenyls on placental steroidogenesis. METHODS: Explants of human placental tissue were used to test differences in PCBs accumulation and influence on placental steroidogenesis. Delor 103 or 106, were added daily for six days at a dose of 200 pg from day 0 to day 6 of culture. The media in the control and experimental groups were changed every day, and collected and frozen for steroid analysis by RIA. Determinations of PCBs of tissue and medium were analysed by GC/MS/MS. RESULTS: Delor 103 was found at a higher level in the tissue than Delor 106. The first day of exposure to Delor 103 had no effect on the conversion of dehydroepiandrosterone (DHEA) to estradiol (E2) while there was a 2-fold decrease in E2 secretion from days 3 to 6. Conversely, Delor 106 caused an immediate increase in E2 secretion, which was maintained at higher levels throughout the exposure period. CONCLUSION: Differences between the accumulation of lower chlorinated and higher chlorinated biphenyls in human placental tissue and in the properties of the congeners can have multiple effects that may intensify or counteract the effects on uterine contraction by PCBs.

Time- and tissue-dependent polychlorinated biphenyl residues in hairless mice after exposure to polychlorinated biphenyl-contaminated soil.

Four groups of 16 age-matched female Crl:SKH1-hrBR hairless mice were exposed to either control soil or polychlorinated biphenyl (PCB)-contaminated soil (retrieved from an electrical waste landfill in Southern Illinois) for 11 weeks. The mice were exposed in a study to determine interactions between environmental PCBs and ultraviolet radiation (UVR), but the UVR group did not differ and provided a replicate for the residue study. Ear biopsies were performed immediately after the termination of soil exposure. The mice were maintained in regular bedding for 37 weeks thereafter. The ear-skin, trunk-skin, fat-pad, and liver samples were collected and weighed at the end of the study (week 48) and analyzed for PCB residues. A total of 141 PCB congeners were target analytes. There were significant differences in body weights and food consumption from week 2 to 28. The liver weights of mice treated with PCB only were significantly greater than those of UVR-treated mice. The fat-pad weight did not differ among treated groups. PCB residues in the ear biopsies specimens of mice exposed to contaminated soil were 342.3 and 317.2 ppm in the PCB- and PCB + UVR-treated groups, respectively, and contained both persistent and episodic congeners. After 37 weeks of isolation from soil, the ear PCB residues decreased to 21.5 ppm (PCB group) and 14.5 ppm (PCB + UVR group), and only persistent congeners contributed to the total PCB residues. The accumulation of PCB residues was highest in the fat pad (fat pad > ear skin > trunk skin > liver) in both PCB +/- UVR groups at the end of the study. However, the percentage of individual congeners contributing to total PCBs in these different tissues did not differ.

Biological effects of gestational and lactational PCB exposure in neonatal and juvenile C57BL/6 mice.

The purpose of this study was to obtain a better understanding of polychlorinated biphenyl (PCB) immunotoxicity in the developing mouse. Adult female mice were dosed with three subcutaneous injections per week of 50 mg/kg Aroclor 1242 (A1242), Aroclor 1254 (A1254), or corn oil for 2 weeks and then mated with nondosed males. First-litter pups were sacrificed at 7 or 28 days of age. At both ages, the tissue concentration of PCB was significantly higher in both the A1242 and A1254 pups than in oil-treated controls. Seven-day-old pups exposed to A1242 or A1254 had significantly decreased splenic IL-2 production. Alterations in the percentages of T cell subsets compared to controls were observed in A1242-exposed pups; an increased spleen somatic index was noted only in A1254-exposed pups. Twenty-eight-day-old pups exposed to A1254 demonstrated a significant decrease in thymus somatic index, an increase in liver somatic index, a 25% decrease in total circulating T(4), and decreased B cell percentages relative to their controls. Alteration in the percentages of CD3(int) T cells was observed in A1254-exposed 28-day-old pups. A significant increase in 7-ethoxyresorufin- O-deethylase (EROD) and 7-benzoxyresorufin-O-dearylase (BROD) activity was measured at both ages in A1254-exposed pups and in A1242-exposed 28-day-old pups. These data confirm that during gestation and lactation A1242 and A1254 are transferred from dams to pups and that such exposure results in immune-related effects in neonatal (7-day-old) and juvenile (28-day-old) mice. Furthermore, A1254 exposure produces more frequent and pronounced effects than exposure to A1242.

Persistent organic pollutants in food supplies.

Persistent organic pollutants (POPs) in various food supplies have important health impacts, but are not as devastating as malnutrition and, perhaps, obesity. POPs should be controlled and the Stockholm Convention is having an accelerating effect on the global decline of POP manufacture and use. Reservoirs from previous misuses are much larger than current manufacture and efforts should be directed at containing these reservoirs, tackling food shortages, and continuing to educate toward following advisories and maintaining a varied diet and food sources.

Sweat chloride: quantitative patch for collection and measurement.

OBJECTIVE: To compare two quantitative pilocarpine iontophoresis tests for sweat chloride. DESIGN: Simultaneous right and left arm sweat tests were done with the Gibson/Cooke and the CF quantum technologies. SETTING: Sweat tests were performed in a quality controlled cystic fibrosis (CF) sweat test laboratory by an experienced technologist at the University of Minnesota CF Center. PATIENTS: Patients referred for sweat tests as well as volunteer CF and control subjects (50 CF and 114 'normals') were tested. INTERVENTIONS: Standard procedures were used for the Gibson/Cooke test (GCST). The manufacturer of the CF quantum test (CFQT) provided factory standardized materials. MAIN OUTCOME MEASURES: Sweat chloride concentration, test time, failed tests, sensitivity, specificity, and cost. RESULTS: Duplicate test comparing the CFQT and the GCST revealed good comparability (R2 = 0.9434). Sensitivity and specificity of the two methods are comparable at about 94% and 99% respectively. Rate of failed tests was 1% for the CFQT and 15% for the GCST. The CFQT and the GCST are comparable (R2 = 0.9434). Sensitivity (94%) and specificity (99%) are the same for both tests. CONCLUSIONS: The CFQT method is equal in accuracy and reliability to the more labor-intensive and costly GCST. Advantages of the CFQT are: the small sample size required (three to ten mg), decreased operator dependence, simpler to perform, and requires less equipment. It could be used in a clinic setting to diagnose CF in patients with suggestive symptoms.

[Discoid lateral meniscus. The importance of MRI scanning for the diagnosis]. / Diskoid lateral menisk. MR-scannings betydning for diagnostik.

This article reports a case of a complete discoid lateral meniscus with an anteriomedial cleavage tear in a 4-year-old boy diagnosed by MRI. The patient underwent arthroscopy with findings of a torn complete discoid lateral meniscus. As the peripheral rim of the meniscus was stable, a partial meniscectomy with reshaping was done. At follow-up two years postoperatively, the patient had recovered uneventfully.

[Subscapular elastofibroma]. / Subskapulaert elastofibrom.

Elastofibroma dorsi (EF) is a rare and benign connective-tissue tumour, typically localized between the lower part of the scapula and the chest wall. Two case stories of EF are presented. The etiology, symptoms, diagnostics and treatment are discussed.

Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study.

The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High-risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five-hundred and ninety-five high-risk infants were identified. High-risk infants were defined as having biparental atopy, or a single atopic first-degree relative combined with cord blood immunoglobulin E (IgE)> or =0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively. If breast-feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products. and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk-based formula were given when needed. All infants were followed-up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to noncompliance. Of 478 infants who completed the study, 232 were exclusively breast-fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast-feeding was high; only eight (2%) children were not breast-fed at all. The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental-reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p=0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast-fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7%(four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p=0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency ofatopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.

Differential and non-uniform tissue and brain distribution of two distinct 14C-hexachlorobiphenyls in weanling rats.

Excretion and tissue retention of a coplanar and a non-coplanar hexachlorobiphenyl (HxCB) were determined 48 h after a single intraperitoneal (ip) dose of 8 mg/kg radiolabeled [14C]-HxCBs to weanling male and female Long-Evans rats. The objective was to understand the involvement of initial target organs of chlorobiphenyl (CB) accumulation following acute exposure in immature animals. During the short interval, both HxCBs remained sequestered predominantly in mesenteric fat (compared to subcutaneous fat) and less than 1% of the doses were excreted. Excretion was 4- to 8-fold lower than adult rats. Coplanar CB 169 (3,3',4,4',5,5'-HxCB) did not accumulate appreciably in the brain, but was retained at 3-fold higher levels in the liver than was non-coplanar CB 153 (2,2',4,4',5,5'-HxCB). Accumulation of 14C-CB 153 in brains was 4- to 9-fold higher than that of 14C-CB 169 and was adequate to detect non-uniform distribution in serial cryostat sections by phosphor imaging autoradiography. The autoradiographs showed a higher CB 153-derived radioactivity associated with fiber tracts throughout the brain. Specifically, the corpus callosum, internal and external capsules, medial lemniscus, tegmentum of the mesencephalon and metencephalon, and cerebellar peduncles showed significantly higher 14C-CB 153 than the other structures. The 14C-CB 153 was not found in the ventricular system and vascular spaces. These results suggest for the first time that an ortho-substituted PCB congener accumulated preferentially in brain in a structure-specific manner when compared to a non-ortho-substituted PCB congener.

Concentrations and frequencies of polychlorinated biphenyl congeners in a Native American population that consumes Great Lakes fish.

OBJECTIVE: Polychlorinated biphenyl congener profiles were examined in serum samples from 61 Native American (Ojibwa) volunteers who regularly consumed fish harvested from the Great Lakes region. A total of 93 peaks are reported which represent 126 individual chlorobiphenyls. RESULTS: When ranked by frequency, 13 peaks comprising single or co-eluting chlorobiphenyls occurred in all 61 samples (a frequency of 100%). These included chlorobiphenyls 138 + 158 + 163, 105 + 132 + 153, 180, 118, 196 + 203, 74, 182 + 187, 199, 183, 114 + 134, 195 + 208, 206, and 194. These 13 peaks also occurred at concentrations higher than those of all other measured chlorobiphenyls, except for the addition of the peak containing chlorobiphenyls 170 and 190, which was below detection in 15% of the samples and ranked fifth in average concentration. The highly chlorinated chlorobiphenyls resembled human serum profiles previously reported in the literature. METHODS: Individual chlorobiphenyls were identified using a gas chromatograph equipped with a 60-meter DB-5 capillary column and electron capture detection. CONCLUSION: When compared to other human residue analyses for fish-eating populations, the Ojibwa samples contained higher proportions of lightly chlorinated and labile chlorobiphenyls such as 8, 16 + 32, 17, 18, 25, 41 + 64 + 71, 33, 52, 110, and 129. These proportions were similar to those found in carp, whitefish, or whitefish livers harvested from the Great Lakes region. These data indicate that regular meals of lower trophic level fish, such as whitefish from the Great Lakes, may distort steady-state human chlorobiphenyl profiles with respect to certain lightly chlorinated or labile chlorobiphenyls.

Immunological, hematological, and biochemical responses in immature white-footed mice following maternal Aroclor 1254 exposure: A possible bioindicator.

A number of hematological, immunological, and biochemical parameters were measured in Peromyscus leucopus pups born from dams exposed to a single dose (300 mg/kg body weight) of Aroclor 1254. To increase the chances of uncovering even modest consequences of the exposure, in one protocol the pups were weaned at 3 weeks and examined at 6 weeks of age, while in a second protocol the pups were kept with their mother for 4 weeks, at which time they were examined. The older pups showed significant decreases in body weight, ratio of spleen weight to body weight, numbers of peripheral white blood cells and lymphocytes, and number and percentage of monocytes. They also showed significant increases in the stimulation index in response to the mitogen phytohemagglutinin (PHA), percentage of peripheral blood neutrophils and liver EROD induction. Pups sacrificed at 4 weeks of age showed even more significant differences. Their body and liver weights, percentage and number of peripheral blood lymphocytes, and serum antibody titers were significantly lower than those of their controls, while spleen to body weight ratios, percent of neutrophils in their peripheral blood, and liver EROD, PROD, and BROD levels were significantly higher than those of the controls. The primary implication of this work is that white-footed mouse pups could be used as biomonitors of contaminated sites. Females could be captured at the sites and bred in captivity with normal males. The vulnerable parameters identified in this study could then be measured in the resulting offspring and compared with a database collected from normal pups.

Changes in thyroid gland morphology after acute acrylamide exposure.

High exposure to the acrylamide monomer has been associated with neuropathy and neurotoxic effects. Chronic lower exposure causes endocrine disruption associated with thyroid, testicular, and mammary tumors. To investigate mechanisms of endocrine disruption, short-term, low-level oral dosing studies were conducted. Weanling female Fischer 344 rats were acclimatized for two weeks before dosing. Controls were given distilled water by gavage and rats in other groups were given acrylamide at doses of 2 mg/kg/day and 15 mg/kg/day for 2 or 7 days by gavage. Twenty-four h after the last dose, the rats were killed by decapitation. Trunk blood was collected for hormone analyses and tissues for histopathological examination. There were no toxicity-related deaths, no clinical signs of toxicity, and no significant difference in the mean body weight of animal groups. Histopathological examination of select tissues showed no lesions of pathologic significance. Plasma thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and pituitary TSH and PRL analyses did not reveal significant changes between control vs. treated rats. In the 7-day study, however, there was a slight dose-dependent increase in plasma T4 and a slight dose-dependent decrease in plasma TSH. Thyroid gland morphometry showed a significant (p < 0.05) decrease in the colloid area and a significant increase (p < 0.05) in the follicular cell height of treated rats as compared to controls. The follicular area shrinkage was similar in both studies. These results show a very early endocrine response to very low levels of toxic insult and opens other venues to further investigate the mechanisms of endocrine disruption by acrylamide.

Toxicity and tissue distribution of 2,2',4,4'- and 3,3',4, 4'-tetrachlorobiphenyls in houseflies.

Insects selectively retain different polychlorinated biphenyls (PCBs) which are then contributed to the food chain. To quantitate specific differences, adult female houseflies (Musca domestica L.) were topically dosed with 0.5 microgram of two structurally distinct PCB congeners (14C-2,2',4,4'-tetraCB or 14C-3,3',4,4'-tetraCB). Total radioactivity in the acetone rinse of intact flies, several tissues, and excrement was determined at 11 time points over a 48-h period. Ninety-seven percent of the applied 2,2',4,4'-tetraCB disappeared from the surface following an initial rapid absorption of 79% within 3 h. The absorbed 2,2',4,4'-tetraCB was immediately found within the thoracic cuticle, then spreading laterally to the abdominal cuticle and head, through the wax layers, or penetrating to the alimentary canal and ovaries. Penetration of 3,3',4, 4'-tetraCB was markedly slower; even though 87% of the applied dose was absorbed within 48 h, only 19% of the dose penetrated into the fly body within the first 3 h. This PCB very slowly distributed into the tissues. Toxicities of the sublethal doses were determined by monitoring changes in activity of houseflies following dosing with 0. 5 microg of radioactive PCBs. Flies treated with 2,2',5-triCB and 3, 3',4,4'-tetraCB remained very active, whereas 2,2',4, 4'-tetraCB-treated flies were less active, consistent with the previously reported toxicity of this congener.

Short-term distribution, metabolism, and excretion of 2,2',5-tri-, 2, 2',4,4'-tetra-, and 3,3',4,4'-tetrachlorobiphenyls in prepubertal rats.

The excretion and tissue retention of three 14C-labeled lower chlorinated biphenyls were examined in prepubertal male and female Sprague-Dawley rats following IV administration. Urine and feces were collected individually at different time intervals up to 72 h for pharmacokinetic analyses. After 72 h, different organs were removed and extracted in acetone:hexane (1:1, v/v) to determine radioactivity. Within the first 10 h after dosing, 2,2', 5-trichlorobiphenyl (PCB 18) was rapidly excreted in urine (8-18% of the administered dose), whereas only 0.6-0.8% of 2,2',4, 4'-tetrachlorobiphenyl (PCB 47) and 0.3-0.8% 3,3',4, 4'-tetrachlorobiphenyl (PCB 77) were found in urine during this time period. The half-life of elimination was shortest for PCB 18 (37.5 to 49.2 h). The half-lives for PCB 47 and PCB 77 were 351 to 672 h and 152 to 186 h, respectively. The cumulative total excretion (urinary + fecal) of PCB 18 within 72 h was 51-62%, of PCB 77 was 22-25%, and of PCB 47 was 7-10%. No parent PCBs were detected in urine. PCB 47 accumulated preferentially in adipose tissues (subcutaneous fat > mesenteric fat); relatively high levels of PCB 47 were also found in adrenals, ovaries, lungs, liver, and skin. The highest concentration of PCB 77 was found in serum, followed by adipose tissues. Very low concentrations of PCB 18 were found in most tissues; the highest being found in serum, followed by ovaries and adrenal glands. This study suggests that prepubertal rats retain higher short-term serum levels and have lower excretion rates than adult rats.

Hematology values from clinically healthy Peromyscus leucopus.

Reported herein are hematocrit and total and differential WBCs obtained from 132 clinically healthy male and female white-footed mice (Peromyscus leucopus) of four different age groups: 4, 5-8, 9-20, and >32 wk old. Minimal differences were identified between the age groups. The number and percentage of neutrophils in the 4-wk-old mice were significantly higher than those in the other groups; the relative percentage of lymphocytes in the 4-wk-old mice was significantly lower than in the 9-20-wk-old mice. The only significant gender effects identified were higher numbers of WBCs and lymphocytes in females of the 4-wk-old group and higher hematocrits in males of the 5-8- and >32-wk-old groups.

Forms and prevalence of intersexuality and effects of environmental contaminants on sexuality in cricket frogs (Acris crepitans).

Cricket frogs (Acris crepitans) from several different sites in Illinois were collected to assess the effects of environmental contamination on the prevalence of intersex gonads. Of 341 frogs collected in 1993, 1994, and 1995, 2.7% were intersex individuals. There was no statistically significant relationship between the chemical compounds detected and cricket frog intersexuality. However, there was an association approaching significance (p = 0.07) between the detection of atrazine and intersex individuals. A comparison of reference sites with sites that had point polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF) contamination revealed a significant relationship between sex-ratio reversal and contamination with PCBs and PCDFs. The sex ratio of juvenile frogs studied from three sites with PCB and PCDF point contamination favored males over females, which was the opposite of the sex ratio in control ponds (p = 0.0007). The statistically significant correlation between organochlorine contamination and sex-ratio reversal suggests PCBs and PCDFs can influence cricket frog sexual differentiation. The current study suggests that in cricket frogs, sex ratios and the prevalence of intersex gonads are altered by environmental contamination.

Hepatic enzyme induction and acute endocrine effects of 2,3,3',4',6-pentachlorobiphenyl in prepubertal female rats.

Polychlorinated biphenyls (PCBs) with the labile 2,3,6-substitution are important components of atmospheric and certain food chain exposures, but little is known about their biological activities. Chlorobiphenyl 110 (2,3,3',4',6-pentaCB) was investigated in weanling female rats dosed ip on days 21 and 22 and killed on day 23 of age. The initial preparation of CB 110 markedly induced 7-ethoxyresorufin O-dealkylase (EROD) activity and was found to be contaminated with coplanar 3,3',4,4',5-pentaCB (CB 126). The contaminated preparation (CB 110C) was purified with activated charcoal (CB 110P). The CB 110P induced pentoxyresorufin O-dealkylase (PROD), was weakly uterotropic and a modest depleter of serum thyroxine (T4). CB 110C caused increased liver weight, induced EROD, PROD, and UDP glucuronyl transferase activities and caused a greater depletion of serum T4; on the other hand, it suppressed the PROD induction and the uterotropic effect of CB 110P. Hepatic residues of CB 110 were a constant 2-3% of the dose while those of CB 126 (from CB 110C) increased with increasing dose to as much as 50% of the dose.