Effects of dietary PCB exposure on adrenocortical function in captive American kestrels (Falco sparverius)

We experimentally examined the effects of dietary exposure to polychlorinated biphenyls (PCBs) on adrenocortical function in American kestrels (Falco sparverius). Nine captive male American kestrels previously exposed to a PCB mixture (Aroclor1248:1254:1260; 1:1:1) in their diet were subjected to a standardized capture, handling and restraint protocol designed to produce an increase in circulating corticosterone. A similar protocol has been applied to a wide range of avian species and was used here to evaluate the response of PCB-exposed and control kestrels to a defined physical stressor. Both baseline and stress-induced corticosterone levels were significantly lower in PCB-exposed birds when compared with control birds of the same age. PCB-exposed birds exhibited significantly lower corticosterone levels during the corticosterone response when compared with control birds, independent of body condition. Furthermore, baseline corticosterone concentrations exhibited a hormetic response characterized by an inverted U-shaped dose response in relation to total PCB liver burden. These results support several recent studies which report decreased levels of circulating corticosterone in PCB-exposed wild birds. The results presented here provide the first evidence that exposure to an environmentally relevant level of PCBs (approximately 10 mg/kg body weight) can impair the corticosterone stress response in kestrels, potentially increasing the susceptibility of birds to environmental stressors such as severe weather and predatory and human disturbance.     

Changes in egg composition of American kestrels exposed to dietary polychlorinated biphenyls

Changes in the quality of eggs of birds exposed to polychlorinated biphenyls (PCBs) have been described, but have never been directly attributed to PCBs. Polychlorinated biphenyl residues in eggs have been associated with reduced reproductive success and embryonic deformities in wild birds. Egg size and composition, specifically the amount of albumen, yolk, and water in an egg, also influence the growth and viability of embryos and hatchlings, and consequently the reproductive success of birds. To deter mine whether PCB exposure of adult birds affected the size and composition of their eggs, 25 pairs of captive American kestrels (Falco sparverius) were fed a mixture of PCB-spiked (1248:1254:1260) food to give an approximate exposure of 7 mg/kg body weight/d, beginning 1 mo prior to pairing, and continuing throughout the courtship, egg-laying, and incubation periods. This dietary level in the adult female kestrels resulted in mean total PCB residues in the eggs of 34.1 microg/g wet weight (geometric mean), which is environmentally relevant. PCB residues in eggs increased with the time of female exposure to the contaminated diet and laying date. Variation in egg size within PCB clutches was significantly greater than within control clutches, although absolute egg mass and volume did not differ markedly by treatment. Only infertile eggs and only one egg per clutch were used for egg composition analysis. Yolks in the PCB-contaminated eggs were heavier, with less wet and dry albumen relative to control eggs. Water content and eggshell thickness were not significantly affected by PCB exposure. These results suggest that eggs from the PCB treatment have relatively more lipid and less protein available for embryonic development. Changes in egg composition were not associated with egg size, lay date, ambient temperature, humidity, or precipitation, which are factors known to affect these variables in bird eggs. The PCB-induced changes in egg composition described here provide insight into possible mechanisms contributing to reduced reproductive performance in wild birds exposed to PCBs.     

The neurotoxicological consequences of developmental exposure to PCBs.

The articles highlighted in this issue are three reports by Kevin Crofton and colleagues dealing with neuromodulatory effects of PCB (Gilbert, Mundy, and Crofton, pp. 102-111; Roegge et al., pp. 121-130; and Crofton et al., pp. 131-140).     

Antibody-mediated immunotoxicity in American kestrels (Falco sparverius) exposed to polychlorinated biphenyls

Antibody-mediated immune function in adult and recently fledged (30 to 33 d old) American kestrels (Falco sparverius) was examined in birds exposed directly, or only in ovo, to polychlorinated biphenyls (PCBs). In 1998, 9 mature male and 9 female kestrels were fed PCBs, whereas 9 females and 10 males served as controls. A mixture of Aroclors 1248:1254:1260 suspended in safflower oil was injected into the kestrels' food items, while in control diets only the same volume of oil was added. The dosage of PCBs was approximately 7 mg/kg kestrel/d, beginning in March 1998 and continuing for 120 d. In 1998, the antibody-mediated immune response was stimulated by immunization and booster vaccinations of the kestrels using a nonpathogenic antigen, dinitrophenol-keyhole limpet hemocyanin (DNP-KLH). In 1999, offspring from three treatment groups based upon maternal exposure to PCBs were similarly tested for their antibody response. None of these mothers was vaccinated with DNP-KLH the previous year. The maternal groups were: (1) exposed to PCBs in 1998 for 120 d, (2) exposed in ovo in 1998 (i.e., mothers were produced by PCB-exposed parents), or (3) unexposed to PCBs. Serum antibody levels were determined using an enzyme-linked immunosorbent assay (ELISA). In 1998, PCB-exposed adult females had a significantly higher antibody response than did controls, whereas adult males exposed to PCBs had significantly suppressed antibody production. For the nestlings produced in 1999, maternal treatment significantly affected antibody response. Generally, the antibody response in the nestlings was much lower than that seen in adult kestrels. Yet both male and female offspring from mothers that had been fed PCBs the previous year had significantly higher postbooster anti-DNP-KLH titers than control and in ovo-exposed maternal groups, thus mimicking the response seen in the adult females the previous year. These sex-specific responses in PCB-exposed birds provide further evidence of the endocrine-disrupting behavior of PCBs. Both suppression and stimulation of the antibody response are undesirable because this indicates that the immune system is not able to respond normally to challenges by infectious or other disease-causing agents.     

Behavior of free-ranging and captive American kestrels under electromagnetic fields

Wild birds, particularly raptors, commonly use electrical transmission structures for nesting, perching, hunting, and roosting. Consequently, birds are exposed to electromagnetic fields (EMFs). The amount of time that wild reproducing American kestrels (Falco sparverius) were exposed to EMFs was determined, and the effects of EMFs on the behavior of captive reproducing kestrels were examined. Wild kestrels were exposed to EMFs for 25% to 75% of the observed time. On a 24-h basis, estimated EMF exposure of wild kestrels ranged from 71% during courtship, to 90% during incubation, similar to that experienced by captive kestrels (88% of a 24-h period). Additionally, captive kestrels were exposed to EMF levels experienced by wild kestrels nesting under 735-kV power lines. Captive EMF females were more active, more alert, and perched on the pen roof more frequently than control females during courtship. EMF females preened and rested less often during brood rearing. EMF male kestrels were more active than control males during courtship, and more alert during incubation. Increased activity of kestrels during courtship may be linked to changes in corticosterone, but likely not melatonin. Observed behavioral changes were unlikely to directly result in the better growth of nestlings and fledging success, or poorer hatching success, of the EMF group, as previously reported. Behavioral changes of captive EMF kestrels may be observed in wild kestrels.     

Developmental toxicity of diphenyl ether herbicides in nestling American kestrels

Beginning the day after hatching, American kestrel (Falco sparverius) nestlings were orally dosed for 10 consecutive days with 5 microliters/g of corn oil (controls) or one of the diphenyl ether herbicides (nitrofen, bifenox, or oxyfluorfen) at concentrations of 10, 50, 250, or 500 mg/kg in corn oil. At 500 mg/kg, nitrofen resulted in complete nestling mortality, bifenox in high (66%) mortality, and oxyfluorfen in no mortality. Nitrofen at 250 mg/kg reduced nestling growth as reflected by decreased body weight, crown-rump length, and bone lengths including humerus, radius-ulna, femur, and tibiotarsus. Bifenox at 250 mg/kg had less effect on growth than nitrofen, but crown-rump, humerus, radius-ulna, and femur were significantly shorter than controls. Liver weight as a percent of body weight increased with 50 and 250 mg/kg nitrofen. Other manifestations of impending hepatotoxicity following nitrofen ingestion included increased hepatic GSH peroxidase activity in all nitrofen-treated groups, and increased plasma enzyme activities for ALT, AST, and LDH-L in the 250-mg/kg group. Bifenox ingestion resulted in increased hepatic GSH peroxidase activity in the 50- and 250-mg/kg groups. Nitrofen exposure also resulted in an increase in total plasma thyroxine (T4) concentration. These findings suggest that altricial nestlings are more sensitive to diphenyl ether herbicides than young or adult birds of precocial species.     

Dietary exposure of the Belgian adult population to non-dioxin-like PCBs

Non-dioxin-like polychlorinated biphenyls (ndl-PCBs), and some of their metabolites, might initiate neurological, neuroendocrinological, immunological and carcinogenic effects. Dietary exposure of the Belgian adult population to ndl-PCBs was investigated in this study. Foods from five food groups, collected in Belgium in 2008, were analyzed by GC–MS/MS for the six indicator PCBs (PCB 28, 52, 101, 138, 153 and 180). Results were expressed as the sum of the six congeners. A dietary exposure assessment was performed, combining ndl-PCBs levels found in food with data from the national food consumption survey of 2004. Fish and fish products were the dominating food group in terms of contamination level, with the highest levels measured in the composite sample «other fishes» (18.58 ng/g FW). The dietary exposure of the Belgian population (n = 3083) to ndl-PCBs ranged from 5.33 ng/kg b.w./day on average to 16.10 ng/kg b.w./day at the 99th percentile, using the lower bound concentration. The mean dietary exposure mainly originates from Fish and fish products (54.3%), followed by dairy products (28.5%). As neither EFSA nor JECFA have set a Tolerable Daily Intake for ndl PCBs, uncertainty remains about how to interpret the exposure data in terms of public health.     

Mitochondrial thiol status in the liver is altered by exposure to hyperoxia

Patients with poorly functioning lungs often require treatment with high concentrations of supplemental oxygen, which, although often necessary to sustain life, can cause lung injury. The mechanisms responsible for hyperoxic lung injury have been investigated intensely and most probably involve oxidant stress responses, but the details are not well understood. In the present studies, we exposed adult male C57/Bl6 mice to >95% O2 for up to 72 h and obtained lung and liver samples for assessment of lung injury, measurements of tissue concentrations of coenzyme A (CoASH) and the corresponding mixed disulfide with glutathione (CoASSG), as possible biomarkers of intramitochondrial thiol redox status. Subcellular fractions were prepared from both tissues for determination of glutathione reductase (GR) activities. Lung injury in the hyperoxic mice was demonstrated by increases in lung weight to body weight ratios at 48 h and by increases in bronchoalveolar lavage protein concentrations at 72 h. Lung CoASH concentrations declined in the hyperoxic mice, but CoASSG concentrations were not increased nor were CoASH/CoASSG ratios decreased, as would be expected for an oxidant shift in mitochondrial thiol-disulfide status. Interestingly, CoASSG concentrations increased (from 6.72+/-0.54 to 14.10+/-1.10 nmol/g of liver in air-breathing controls and 72 h of hyperoxia, respectively, P<0.05), and CoASH/CoASSG ratios decreased in the livers of mice exposed to hyperoxia. Some apparent effects of duration of hyperoxia on GR activities in lung or liver cytosolic, mitochondrial, or nuclear fractions were observed, but the changes were not consistent or progressive. Yields of isolated hepatic nuclear protein were decreased in the hyperoxic mice within 24 h of exposure, and by 72 h of hyperoxia, protein recoveries in purified nuclear fractions had declined from 41.8 to 14.8 mg of protein/g animal body weight. Concentrations of 10-formyltetrahydrofolate dehydrogenase were diminished in hepatic mitochondria of hyperoxic mice. A second protein in hepatic mitochondria of approximately 25 kDa showed apparent decreases in thiol content, as determined by fluorescence intensities of monobromobimane derivatives separated by SDS-PAGE. The mechanisms responsible for the observed effects and the possible implications for the adverse effects of hyperoxic therapies are not known and need to be investigated.     

Macrophage regulation of myelopoiesis is altered by exposure to the benzene metabolite hydroquinone

Hydroquinone, a myelotoxic metabolite of benzene, decreases the ability of murine bone marrow stromal cells to support myelopoiesis in vitro. Bone marrow stroma consists of macrophages and fibroblastoid stromal cells that participate coordinately in regulating myelopoiesis. The goal of this study was to determine if macrophage or fibroblastoid cell function is more sensitive to the myelotoxic actions of hydroquinone. To address this question, we developed purified populations of macrophages and fibroblastoid stromal cells and treated each population with hydroquinone. These cells were reconstituted together with nontreated cells of the opposite type and assayed for their ability to support the formation of granulocyte and macrophage colonies in an agar overlay. Reconstituted cultures containing hydroquinone-treated macrophages supported fewer colonies than did corresponding cultures containing untreated macrophages. Reconstituted cultures containing hydroquinone-treated fibroblastoid stromal cells were not affected. Moreover, hydroquinone reduced detectable interleukin-1 activity in purified macrophage cultures stimulated with lipopolysaccharide. These results indicate that hydroquinone selectively interferes with macrophage function possibly, in part, via alteration of macrophage interleukin-1 secretion.     

NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure to PCBs and TCDD in rats

A metabonomic approach using ¹H NMR spectroscopy was adopted to investigate the metabonomic pattern of rat urine after oral administration of environmental endocrine disruptors (EDs) polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) alone or in combination and to explore the possible hepatotoxic mechanisms of combined exposure to PCBs and TCDD. ¹H NMR spectra of urines collected 24 h before and after exposure were analyzed via pattern recognition by using principal component analysis (PCA). Serum biochemistry and liver histopathology indicated significant hepatotoxicity in the rats of the combined group. The PCA scores plots of urinary ¹H NMR data showed that all the treatment groups could be easily distinguished from the control group, so could the PCBs or TCDD group and the combined group. The loadings plots of the PCA revealed remarkable increases in the levels of lactate, glucose, taurine, creatine, and 2-hydroxy-isovaleric acid and reductions in the levels of 2-oxoglutarate, citrate, succinate, hippurate, and trimethylamine-N-oxide in rat urine after exposure. These changes were more striking in the combined group. The changed metabolites may be considered possible biomarker for the hepatotoxicity. The present study demonstrates that combined exposure to PCBs and TCDD induced significant hepatotoxicity in rats, and mitochondrial dysfunction and fatty acid metabolism perturbations might contribute to the hepatotoxicity. There was good conformity between changes in the urine metabonomic pattern and those in serum biochemistry and liver histopathology. These results showed that the NMR-based metabonomic approach may provide a promising technique for the evaluation of the combined toxicity of EDs.     

Secondary poisoning of kestrels by white phosphorus

Since 1982, extensive waterfowl mortality due to white phosphorous (P4) has been observed at Eagle River Flats, a tidal marsh near Anchorage, Alaska. Ducks and swans that ingest P4 pellets become lethargic and may display severe convulsions. Intoxicated waterfowl attract raptors and gulls that feed on dead or dying birds. To determine if avian predators can be affected by secondary poisoning, we fed American kestrels (Falco sparverius) 10-day-old domestic chickens that had been dosed with white phosphorus. Eight of 15 kestrels fed intact chicks with a pellet of P4 implanted in their crops died within seven days. Three of 15 kestrels fed chicks that had their upper digestive tracts removed to eliminate any pellets of white phosphorus also died. Haematocrit and haemoglobin in kestrels decreased whereas lactate dehydrogenase-L, glucose, and alanine aminotransferase levels in plasma increased with exposure to contaminated chicks. Histological examination of liver and kidneys showed that the incidence and severity of lesions increased when kestrels were fed contaminated chicks. White phosphorus residues were measurable in 87% of the kestrels dying in the study and 20% of the survivors. This study shows that raptors can become intoxicated either by ingesting portions of digestive tracts containing white phosphorus pellets or by consuming tissues of P4-contaminated prey     

Effects of inhalation exposure to a binary mixture of benzene and toluene on vitamin a status and humoral and cell-mediated immunity in wild and captive American kestrels

Benzene and toluene are representative volatile organic compounds (VOC) released during production, storage, and transportation associated with the oil and gas industry and are chemicals of concern, as they are released in greater and possibly more biologically significant concentrations than other compounds. Most studies of air pollution in high oil and gas activity areas have neglected to consider risks to birds, including top-level predators. Birds can be used as highly sensitive monitors of air quality and since the avian respiratory tract is physiologically different from a rodent respiratory tract, effects of gases cannot be safely extrapolated from rodent studies. Wild and captive male American kestrels were exposed for approximately 1 h daily for 28 d to high (rodent lowest-observed-adverse-effect level [LOAEL] of 10 ppm and 80 ppm, respectively) or environmentally relevant (0.1 ppm and 0.8 ppm, respectively) levels of benzene and toluene. Altered immune responses characteristic of those seen in mammalian exposures were evident in kestrels. A decreased cell-mediated immunity, measured by delayed-type hypersensitivity testing, was evident in all exposed birds. There was no effect on humoral immunity. Plasma retinol levels as measured by high-performance liquid chromatography (HPLC) analysis were decreased in wild and captive kestrels exposed to the rodent LOAEL for combined benzene and toluene. This study indicates that American kestrels are sensitive to combined benzene and toluene. The study also illustrates the need for reference concentrations for airborne pollutants to be calculated, including sensitive endpoints specific to birds. Based on these findings, future studies need to include immune endpoints to determine the possible increased susceptibility of birds to inhaled toxicants.     

Atrazine exposure leads to altered growth of HepG2 cells

Atrazine is one of the most commonly used herbicides in the United States. While effective on target plants, it has been associated with harmful health effects in non-target organisms such as fish, amphibians and mammals. In this study, growth effects on human liver cells were determined after exposure to increasing concentrations of this herbicide. Growth of immortalized human hepatoma HepG2 cells was inhibited by atrazine concentrations of 625 ppb after 72 h exposure and flow cytometry analysis demonstrated HepG2 cells exposed to 100 ppb atrazine accumulated in S phase after 48 h compared to untreated cells. Expression of cell cycle specific cyclin proteins was altered after atrazine exposure with cyclin E levels significantly decreased after a 24 h exposure and cyclin B levels decreased after 48 h. This study demonstrates that relatively low levels of atrazine exposure can affect growth and lead to disruptions in the cell cycle regulation of immortalized human liver cells.     

Changes of urinary and blood porphyrin profiles by exposure to PCBs,lead or diazinon in rats

Porphyrin profiles in excreta or blood have been useful biomarkers for monitoring exposure of hazardous xenobiotics to human or animals. We evaluated and compared the changes in urinary and blood copro-, uro-, and protoporphyrins during and after the exposure of Aroclor1254 (PCBs), lead (Pb) or diazinon to rats. PCBs (10, 50 and 100 mg/kg bw), Pb (62.5, 250 and 1,000 ppm) and diazinon (10, 30 and 90 mg/k bw) were administered to rats via gavage (PCBs and diazinon) or via drinking water (Pb) daily for 5 w. Urine and blood were collected weekly for the 5 w of exposure and for 5 w after withdrawal. Three urinary porphyrins and blood protoporphyrin increased gradually with PCB dose in a time dependent manner and remained elevated for 5 w after withdrawal. Urinary porphyrins were increased rapidly by Pb and then returned to normal immediately after Pb withdrawal while blood protoporphyrin remained high but gradualy decreased during the 5 w after withdrawal. Diazinon did not affect blood and urinary porphyrins as did PCBs and Pb, but just induced a weak increase of urinary coproporphyrin. Urinary and blood porphyrin profiles can be used as biomarkers for exposure assessment to PCBs and Pb. The normal ranges of blood porphyrins in cattle, pigs, chickens and rats were also established for use as biomarkers.     

Dietary exposure to dioxins and dioxin-like PCBs in The Netherlands anno 2004

In this study, representative occurrence data for PCDD/Fs and dioxin-like PCBs in food were obtained and used to estimate dietary exposure of the Dutch population. Food composite samples were analyzed as well as single fish and vegetables samples. Total dioxin concentrations in animal products ranged from 0.05 pg TEQ/g product in poultry to 2.5 pg TEQ/g product (using TEF(2006)) in fish (shrimp), with 0.12pg TEQ/g product being the lowest concentrations measured in fish (tuna). In vegetable products, concentrations ranged from 0.00002 pg TEQ/g product (white kale) to 0.19 pg TEQ/g (oils and fats). A long-term dietary exposure distribution was calculated using Monte Carlo Risk Assessment software. The lower bound median exposure of the Dutch population to PCDD/Fs and dioxin-like PCBs was estimated at 0.8 pg WHO-TEQ/kgbw/d, half of which were dioxin-like PCBs. Dairy was the main source (38%) due to its high consumption. Time-trend analysis shows that the exposure to dioxins has further decreased by 35% over the past five years. This is due to lower levels of dioxin-like compounds in most of the foods, mainly influenced by lower levels in meat and milk. The use of the new TEFs gives an exposure reduction of 10% with respect to TEF(1998). Still, 4% of the Dutch population exceeds the exposure limit of 14 pg/kgbw/week as set by the EU.     

Changes in plasma retinol of American kestrels (Falco sparverius) in response to dietary or in ovo exposure to environmentally relevant concentrations of a penta-brominated diphenyl ether mixture, DE-71

Polybrominated diphenyl ethers (PBDE) are ubiquitous, lipophilic, and bioaccumulative brominated flame retardants. Plasma retinol concentrations of captive adult American kestrels were assessed at the beginning of the breeding season following 3 wk of daily dietary exposure to vehicle (control), low (0.3 ng/g wet weight [ww]), or high (1.6 ng/g ww) concentrations of DE-71 and in their 25-d-old nestlings following embryonic exposure by maternal deposition to environmentally relevant low (291 ± 48 ng/g ww) or high (1111 ± 160 ng/g ww) sum (Σ) PBDE concentrations. Unexpectedly, low in ovo concentrations of total-α-hexabromocyclododecane (HBCD) were detected. Plasma retinol concentrations of adult males exposed to higher DE-71 concentrations were negatively correlated with in ovo ΣPBDE, BDE-100, and HBCD levels. Maternal (13%) and nestling (11%) retinol levels were lower in the low-exposure group compared to respective controls, and biologically significant since their retinol levels were correlated with hatching success and growth, respectively. Maternal retinol levels were also correlated with BDE-153. The underlying mechanisms may involve (1) PBDE exposure, hydroxylated (OH-) metabolites, and subsequent changes in retinol mobilization; (2) decreased maternal food consumption; and (3) reduced maternal retinol yolk deposits. The apparent lack of retinol changes in the high-exposure kestrel may reflect compensation occurring, either by increased mobilization and transportation of retinol, and/or higher food consumption in these birds. When highly mobile as evidenced during reproduction or development, retinol concentrations of adult and nestling kestrels are sensitive to environmentally relevant PBDE and HBCD levels.     

Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin

Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro‐inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro‐inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 ? 2.5 nM) and DBT (5 ? 0.05 µM) in highly enriched human NK cells, a monocyte‐depleted preparation of PBMCs, and monocyte‐containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 559–571, 2015.     

Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure.

Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.     

Effects of exposure to PCBs and related compounds on growth and activity in children

Two hundred thirty-six children from two established cohorts at risk for exposure to polychlorinated biphenyls (PCBs) and related contaminants were evaluated at age 4 years. Prenatal exposure (assessed by cord serum PCB level) was associated with lower weight, an effect consistent with reports of growth retardation in laboratory rats and in children exposed at high levels in Taiwan and at general population levels in Japan. The highest exposed children weighed 1.8 kg less on the average than the least exposed. Contemporary body burden (assessed by 4-year serum PCB level) was associated with reduced activity based on composite ratings provided by the child's mother and two independent examiners. This effect, attributable to lactation exposure, was strongest among the offspring of women with above average milk PCB levels who breast fed for at least 1 year. While the weight deficit is consistent with previous data linking developmental effects of low-dose human PCB exposures specifically to the prenatal period, activity is the first domain found to be affected by lactation at contemporary levels of exposure.