Developmental Toxicity of PCB 126 (3,3',4,4',5-Pentachlorobiphenyl) in Nestling American Kestrels (Falco sparverius)

Planar PCB congeners are embryotoxic and teratogenic to birdsincluding American kestrels. The developmental toxicity of 3,3',4,4',5-pentachlorobiphenyl(PCB 126) was studied in the posthatching kestrel as a modelfor the eagle. Nestlings were dosed orally for 10 days with5 µl/g body weight of corn oil (controls) or the planarPCB 126 at concentrations of 50, 250, or 1000 ng/g body weight.Dosing with 50 ng/g of PCB 126 resulted in a hepatic concentrationof 156 ng/g wet weight, liver enlargement and mild coagulativenecrosis, over 10-fold increases in hepatic microsomal ethoxyresorufin-O-dealkylaseand benzyloxyresorufin-O-dealkylase, and approximately a 5-foldincrease in methoxyresorufin-O-dealkylase. At this dose, mildto moderate lymphoid depletion of the spleen was apparent, aswere decreased follicle size and content of the thyroid. At250 ng/g, concentration of PCB 126 in the liver was 380 ng/gwith increasing multifocal coagulative necrosis, decreased bonegrowth, decreased spleen weight with lymphocyte depletion ofthe spleen and bursa, and degenerative lesions of the thyroid.At 1000 ng/g, the liver concentration was 1098 ng/g, accompaniedby decreased bursa weight, decreased hepatic thiol concentration,and increased plasma enzyme activities (ALT, AST, and LDH-L)in addition to the previous effects. Highly significant positivecorrelations were noted between liver concentrations of PCB126 and the ratio of oxidized to reduced glutathone. These findingsindicate that nestling kestrels are more susceptible to PCB126 toxicity than adults, but less sensitive than embryos, andthat planar PCBs are of potential hazard to nestling birds.     

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.     

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.     

Reproductive abnormalities, teratogenicity, and developmental problems in American kestrels (Falco sparverius) exposed to polychlorinated biphenyls

This study found abnormalities in multiple reproductive stages in captive American kestrels (Falco sparverius) when exposed to polychlorinated biphenyls (PCBs) through dietary and in ovo exposure. American kestrels laid eggs with environmentally relevant total PCB levels (34.1 micrograms/g whole egg wet weight) when consuming PCB-spiked (Aroclor 1248:1254:1260) food (5-7 micrograms/g body weight per day) for 100 d only in 1998. In 1999, the same adults laid eggs with estimated total PCBs of 23 micrograms/g. Effects of maternal (only female exposed) and paternal (only male exposed) in ovo PCB exposure were investigated. Maternal F1 eggs contained predicted total PCB concentrations of 0.34 microgram/g. Specific abnormalities occurred more frequently during dietary F0 exposure, particularly aggressive courtship interactions, clutch abandonment, occurrences of cracked eggs, and developmental effects. Multiple developmental effects were more pronounced during than after dietary PCB exposure of adults, and although these effects were limited, nevertheless they occurred in the F1 maternal and F1 paternal pairs. However, the incidence of multiple deformities throughout the breeding season increased dramatically from 1998 (13%) to 1999 (56%) in F0 PCB-exposed pairs. Developmental abnormalities were unlikely to be attributed to the extrinsic factors of disease, genetics, or nutritional (vitamin D3) deficiencies, but rather to adverse changes in parental behavior and intrinsic factors involving altered genetic material and PCB exposure. Readily cleared PCB congeners may induce specific types of behavioral and developmental abnormalities, but persistent congeners and metabolites are likely producing (1) odd laying patterns, (2) odd laying patterns, (2) developmental effects including embryonic underdevelopment and edema, and (3) increased incidences of multiple deformities within a clutch.     

Changes in the growth, but not the survival, of American kestrels (Falco sparverius) exposed to environmentally relevant polybrominated diphenyl ethers

Polybrominated diphenyl ether (PBDEs) concentrations are increasing exponentially in biota. We studied the growth of American kestrel (Falco sparverius) nestlings exposed in ovo and during development to environmentally relevant PBDE congeners and concentrations. Eggs within each clutch, divided between groups by laying sequence, were injected into the air cell at 19 days of incubation with safflower oil or penta-BDE congeners BDE-47, -99, -100, and -153 dissolved in safflower oil (18.7 microg total sigmaPBDEs/egg), approximating current levels in Great Lakes herring gulls. The measured proportions of BDE congeners found in the dosing oil were 56.4% of BDE-47; 27.2% of BDE-99; 24.8% of BDE-100; and 0.6% of BDE-153. For 29 days, nestlings were orally gavaged daily with the same sigmaPBDE mixture (15.6 +/- 0.3 ng/g body weight/day). Relative congener abundances in the dosing mixture compared to the carcasses suggest biotransformation of BDE-47; BDE-183 was also detected. PBDE exposure did not affect hatching or fledging success. PBDE-exposed nestlings were larger (weight, bones, feathers) as they gained weight more quickly and ate more food, the latter in association with their SigmaPBDE body burdens. BDE-100 was most influential on nestling growth, being positively associated with size, weight gain, and food consumption. Increasing concentrations of BDE-183 and -153 were related to longer bones, and BDE-99 to longer feathers. The larger size of the PBDE-exposed birds may be detrimental to their bone structure and have excessive energetic costs. The repeated relationships with BDE-100 and growth may be important for wild Falconidae, since this is the predominant penta-BDE congener in these raptors.     

Exposure to polybrominated diphenyl ethers (PBDEs): changes in thyroid, vitamin A, glutathione homeostasis, and oxidative stress in American kestrels (Falco sparverius).

Polybrominated diphenyl ethers (PBDEs), a class of additive flame retardants, are temporally increasing in wildlife tissues and capable of disrupting normal endocrine function. We determined whether in ovo and post-hatch exposure of captive American kestrels (Falco sparverius) to environmentally relevant PBDEs alter thyroid, retinol, and oxidative stress measures. Control eggs were injected with safflower oil and subsequent nestlings fed the same vehicle; dosed eggs received PBDE congeners (BDE-47, -99, -100, -153), which mainly comprise the Penta-BDE commercial mixture, dissolved in safflower oil at concentrations (1500 ng/g total [Sigma] PBDEs) approximating those in Great Lakes gull eggs. Nestlings hatching from dosed eggs were orally exposed for 29 days to variable SigmaPBDE concentrations that are similar to levels reported in tissues of Great Lakes trout (100 ng/g). Treatment kestrels had lower plasma thyroxine (T(4)), plasma retinol, and hepatic retinol and retinyl palmitate concentrations, but unaltered triiodothyronine (T(3)) concentrations and thyroid glandular structure. BDE-47, -100, and -99 were negatively associated with plasma T(4), plasma retinol (BDE-100, -99) and hepatic retinol (BDE-47). Despite an antioxidant-rich diet, PBDE exposure induced hepatic oxidative stress, particularly in females, with an increased hepatic GSSG:GSH ratio, a marginal increase in lipid peroxidation, and increased oxidized glutathione. Positive associations were found between concentrations of BDE-183 and thiols and, in males, between BDE-99 and reduced GSH, but a negative association occurred between BDE-99 and TBARS. Subsequently, concentrations of PBDE congeners in wild birds may alter thyroid hormone and vitamin A concentrations, glutathione metabolism and oxidative stress.     

Hepatic Porphyrin Synthesis in Rats After Pretreatment with Polychlorinated Biphenyls (PCBs)

Abstract: A single dose of polychlorinated biphenyls caused an increase of δ-aminolevulinic acid synthetase activity and porphyrin content in rat liver. δ-aminolevulinic acid dehydratase activity was not altered significantly. A maximum effect was obtained 24 hrs after treatment, and the rate limiting enzyme of porphyrin synthesis returned to a normal level of activity at the third day after treatment. On the contrary the porphyrin content of the liver remained elevated up to 4 weeks after a single injection of polychlorinated biphenyls. After administration of polychlorinated biphenyls the kinetic properties of δ-aminolevulinic acid synthetase of rat liver were found to be altered: an increase of V_max was accompanied by a decrease of K_m. The threshold dose for an increase of δ-aminolevulinic acid synthetase activity and porphyrin content of rat liver after a single dose of polychlorinated biphenyls was about 0.019 mmol/kg body weight for starved animals. At this dose range no significant differences in response of the parameters examined were seen when polychlorinated biphenyls with variable chlorine contents were administrated. A maximum effect for δ-aminolevulinic acid synthetase was obtained by a threefold dose, and no further increase was obtained by much higher doses, whereas increasing response up to these high doses was seen for the porphyrin content of the liver. At high doses the activity of δ-aminolevulinic acid synthetase increased with increasing chlorine content of the polychlorinated biphenyls.     

Annual abundance of common Kestrels (Falco tinnunculus) is negatively associated with second generation anticoagulant rodenticides

Ecotoxicology - Rats and mice can damage food and agricultural products as well as transmit diseases, thereby requiring control of their numbers. Application of Second Generation Anticoagulant...     

Human Exposure to Polychlorinated Biphenyls and Health Effects

Polychlorinated biphenyls (PCBs) are a mixture of chemicals. Some congeners of the mixture are highly persistent both in the environment and in humans. Although PCBs have not been used commercially since about 1977 in the US, they can still be detected in human blood and tissues in this country. PCB levels are declining and are often no longer detectable in younger people. A cursory review of recent animal studies is provided. Studies to determine whether PCBs cause cancer in humans, neurobehavioural effects, abnormal thyroid and immune function in children and low birth weight are discussed in more detail. These studies are inconclusive and do not provide clinical evidence that PCBs at levels encountered with human exposure produce adverse health effects. The differences in PCB blood or tissue concentrations between controls and cases, or between the upper and lower end of various environmentally exposed groups of children or adults, are small. Although some effects are statistically significantly different, they do not appear to be biologically significant. Many studies on the effects of PCBs are difficult to interpret because the range of normal values for clinical and neurobehavioural tests are not provided or appropriately considered, there was no, or inadequate, control for potential confounders. In occupational mortality studies, exposures were much higher. In some studies, various specific cancers were elevated. However, these appear to be chance observations resulting from multiple comparisons since the increase of specific cancers was not consistent between studies and was no longer present in some cohorts when studies were repeated at a later date with longer follow-up. Overall, the data fail to demonstrate conclusive adverse health effects of PCBs at concentrations encountered with human exposures.     

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.     

Induction of the Drug Metabolizing System in Rainbow Trout (Salmo gairdnerii) Liver by Polychlorinated Biphenyls (PCBs)

Abstract Clophen A50 is shown to enhance the O–demethylation of p–nitroanisole to p–nitrophenol and to elevate the cytochrome P–450–content of the rainbow trout liver. Three days after feeding, the O–demethylating activity had increased about 4–fold while the cytochrome P–450–concentration was unchanged. This suggests that the process is divided into two or more steps, with an initial lag in the cytochrome P–450 formation. From 7 days and throughout the experiment a concomitant increase in the O–demethylating activity and the cytochrome P–450–content can be observed. The increased activity can not, however, be solely correlated to the increase in cytochrome P–450 content.     

Effects of Polychlorinated Biphenyls (PCBs) on Brain Tyrosine Hydroxylase Activity and Dopamine Synthesis in Rats

Literature reports suggest that polychlorinated biphenyls (PCBs)may alter dopaminergic neurotransmission in mammalian forebrain.In vitro, PCBs can decrease dopamine levels in PC 12 cells andstudies of the structure-activity relationship (SAR) indicatethat ortho-substituted (non-coplanar) PCB congeners are moreactive than para-substituted (coplanar) congeners. This reporttested the hypothesis that ortho-substituted PCBs can selectively(vs para-substituted congeners) decrease dopamine synthesisin mammalian forebrain by inhibiting the activity of tyrosinehydroxylase, the rate-limiting enzyme in dopamine biosynthesis.In vitro effects of individual PCB congeners on activity ofstriatal tyrosine hydroxylase from two different rat strainswere assessed. It was found that certain ortho-substituted PCBcongeners (e.g., 2,2'-DCB) can inhibit tyrosine hydroxylaseactivity and dopamine synthesis by nearly 40% in minces of corpusstriatum prepared from Sprague-Dawley and Long-Evans hoodedrats. Comparatively, the ortho,meta-substituted PCB congener2,2',5,5'-TeCB inhibited tyrosine hydroxylase activity onlyin striatal minces obtained from Sprague-Dawley rats, suggestingthat genetic factors may influence the susceptibility of mammalsto effects of PCBs that compromise brain dopamine synthesis.The PCB-induced inhibition of tyrosine hydroxylase activityin mammalian forebrain observed here appears to occur throughindirect and as yet unknown mechanisms.     

Semi Permeable Membrane Device Reveals Indoor and Outdoor Contamination of Polychlorinated Biphenyls (PCBs)

Semi Permeable Membrane Device (SPMD) was deployed on an experimental basis for five days inside an Environmental Chemistry Laboratory and two sites outside the building in Kiel, Germany to understand the time-averaged contaminant profiles and concentrations of PCBs. Multi Dimensional High Resolution Gas Chromatography-Electron Capture Detection technique and high resolution clean up techniques were employed to SPMD derived triolein samples. Air concentrations were derived from well established mass transfer coefficients or rate constants for PCBs in SPMD. PCBs profiles in indoor and outdoor samples were distinctly different, exemplified by a particle free clean-up laboratory facility where particle associated higher chlorinated congeners were absent. SPMDs revealed the ‘occupational hazard’ to workers inside the building from chemical contamination derived from both building materials and chemicals used in the laboratory. Finger printing technique using principle component analysis (PCA) revealed that PCB contamination was derived from German commercial PCB mixtures. SPMD derived air concentrations in outdoor samples resembled levels recorded by similar devices in Europe. Ultimately, a simple sampling technique in combination with high resolution analytical techniques demonstrated the uptake of more than 60 PCB congeners within a short period of time.     

Dioxin-Like and Non-Dioxin-Like Toxic Effects of Polychlorinated Biphenyls (PCBs): Implications For Risk Assessment

Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative, and toxic contaminants in the environment. Individual PCB congeners exhibit different phy sicochemical properties and biological activities that result in different environmental distributions and toxicity profiles. The variable composition of PCB residues in environmental matrices and their different mechanisms of toxicity complicate the development of scientifically based regulations for the risk assessment. In this article various approaches for the assessment of risks of PCBs have been critically examined. Recent developments in the toxic equivalency factor (TEF) approach for the assessment of toxic effects due to dioxin-like PCBs have been examined. PCB exposure studies that describe non-dioxin-like toxic effects, particularly neurobehavioral effects and their effective doses in animals were compiled. A comparative assessment of effective doses for dioxin-like and non-dioxin-like effects by PCBs has been made to evaluate the relative significance of non-ortho-and ortho-substituted PCBs in risk assessment. Using mink as an example, relative merits and implications of using TEF and total PCB approaches for assessing the potential for toxic effects in wildlife was examined. There are several advantages and limitations associated with each method used for PCB risk assessment. Toxic effects due to coplanar PCBs occur at relatively smaller concentrations than those due to non-dioxin-like PCBs and therefore the TEF approach derives the risk assessment of PCBs, in the environment. The need for the refinement of TEF approach for more accurate assessment of risks is discussed.     

Immunotoxicity of Technical Pentachlorophenol (PCP-T): Depressed Humoral Immune Responses to T-dependent and T-independent Antigen Stimulation in PCP-T Exposed Mice

Immunotoxicity of Technical Pentachlorophenol (PCP-T): DepressedHumoral Immune Responses to T-dependent and T-independent AntigenStimulation in PCP-T-Exposed Mice. Kerkvliet, N.I., Baecher-Steppan,L., Claycomb, A.T., Craig, A.M. and Sheggeby, G.G. (1982). Fundam.Appl. Toxicol 2:90–99. The effects of chronic dietaryexposure to technical pentachlorophenol (PCP-T) on humoral immuneresponses in mice were examined. Primary and secondary splenicantibody responses to the T-dependent antigen, sheep red bloodcells (SRBC), were examined in Swiss-Webster mice using ourrecently developed screening technique, the Hemolytic AntibodyIsotope Release (HAIR) assay. To assess direct effects of PCP-Ton B cells, the splenic plaque-forming cell response and serumantibody titers to the T-independent antigen, dinitrophenyl(DNP)-Ficoll, were examined. PCP-T exposure altered both thekinetics and the magnitude of the humoral antibody responsesto SRBC and DNP-Ficoll. Peak splenic antibody production andserum antibody titers were delayed and the magnitude of theantibody responses were dose-dependently suppressed by PCP-Texposure. IgM responses appeared to be more sensitive to PCP-T-inducedsuppression than the IgG response. Significant depression ofthe IgM anti-SRBC splenic HAIR response was apparent as earlyas 2 weeks after initiation of PCP-T exposure and persistedfor at least 8 weeks after termination of PCP-T feeding. Liverweight and serum lactate dehydrogenase (LD-L) and alanine aminotransferase(ALT) levels were significantly elevated during PCP-T exposureand returned to control levels after a 4–6 week recoveryperiod. The immunotoxic effect of PCP on humoral immunity wasobserved only in animals exposed to technical grade PCP knownto be contaminated with significant levels of other chlorinatedphenols as well as non-phenolic impurities including chlorinateddioxins, furans, and diphenyl ethers. Animals exposed to analyticalgrade PCP did not exhibit depressed humoral immunity.     

多氯联苯对大鼠脾脏EROD的诱导作用

本文报告用多氯联苯(PCB)200mg/kg对大鼠连续腹腔注射三日染毒,除可诱导肝脏微粒体乙氧基异吩噁唑脱乙基酶(EROD)活性增高外,在脾脏微粒体内也检出EROD活性(4.9pmol/min·mg蛋白质)。当PCB剂量为400mg/kg时,大鼠脾脏S_9组分中EROD活性为对照组的3.3倍。结果说明尽管脾脏本底的细胞色素P-448活性极低,但仍可被化学致癌物PCB诱导。     

GC-MS/MS测定中药中18种多氯联苯

目的 建立GC-MS/MS测定中药材中18种多氯联苯（PCBs）的方法。方法 采用超声提取,浓硫酸净化,内标法定量;采用EI源,在多反应监测（MRM）模式下进行检测。结果 18种PCBs在0.5~50 ng·L^-1时线性关系良好,相关系数（r）为0.999 8~1.000 0,方法的检出限为0.013~0.080 μg·kg^-1,定量限为0.054~0.328 μg·kg^-1。在2,5,10 μg·L^-1下平均回收率分别为106.7%~118.7%,93.5%~114.7%和89.9%~115.6%,相对标准偏差分别为1.6%~8.0%,2.7%~4.6%和1.0%~3.1%。结论 本方法样品处理简单、快速,灵敏度高,准确性好,可用于中药材中18种PCBs的测定。     

Inhibition of Dye Transfer in Rat Liver WB Cell Culture by Polychlorinated Biphenyls

Abstract: In the present investigation the scrape loading/dye transfer assay and microinjection technique are used in order to investigate inhibition of cell-cell communication induced by different polychlorinated biphenyl (PCB) congeners. In these in vitro assays, inhibition of intercellular communication is directly measured as decreased transfer of a fluorescent dye (Lucifer Yellow CH) from donor cells loaded with the dye to surrounding recipient cells. The results show that substitution in the ortho position from the carbon bridge is essential and at least one chloro substitutent in ortho position is necessary for the ability to inhibit intercellular communication. The results also suggest that an increase in the number of ortho substituted chlorine atoms in the PCB molecule enhances the ability to inhibit intercellular communication. On the other hand, the total number of substitutions may not be crucial for the ability to inhibit intercellular communication. Our results suggest that PCB-induced down-regulation of intercellular communication is a result of a specific mechanism and not due to unspecific membrane pertubation.