Persistence Of Polychlorinated Biphenyls Research Articles

The impact of climate sensitive factors on the exposure to organohalogenated contaminants in an aquatic bird exploiting both marine and freshwater habitats

To assess how climate-sensitive factors may affect the exposure to organochlorines (OCs) and perfluoroalkyl substances (PFASs), we monitored concentrations in eggs of the common goldeneye (Bucephala clangula) over two decades (1999–2019) in central Norway. The goldeneye alternates between marine and freshwater habitats and is sensitive to climate variation, especially due to alterations in ice conditions which may affect feeding conditions. We assessed how biological factors such as diet (stable isotopes δ13C and δ15N), the onset of egg laying, and physical characteristics such as winter climate (North Atlantic Oscillation: NAOw) influenced exposure. We predicted compounds to show different temporal trends depending on whether they were still in production (i.e. some PFASs) or have been banned (i.e. legacy OCs and some PFASs). Therefore, we controlled for potential temporal trends in all analyses. There were declining trends for α- and γ-hexachlorocyclohexane (HCH), oxychlordane, cis-chlordane, cis-nonachlor, p,p′-dichlorodiphenyltrichloroethane (p.p′-DDT) and less persistent polychlorinated biphenyl (PCB) congeners (e.g. PCB101). In contrast, the dominant compounds, such as p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and persistent PCB congeners, were stable, whereas hexachlorobenzene (HCB) increased over time. Most OCs were positively related to δ15N, suggesting higher exposure in birds feeding at upper trophic levels. Chlordanes and HCB were positively associated with δ13C, indicating traces of marine input for these compounds, whereas the relationships to most PCBs were negative. Among PFASs, perfluorooctanesulfonamide (PFOSA) and perfluorohexane sulfonic acid (PFHxS) declined. Most PFASs were positively associated with δ13C, whereas there were no associations with δ15N. Egg laying date was positively associated to perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), suggesting that some of the PFAS load originated from the wintering locations. Although NAOw had little impact on the exposure to organohalogenated contaminants, factors sensitive to climate change, especially diet, were associated with the exposure to OHCs in goldeneyes.

Ecosystem specific accumulation of organohalogenated compounds: A comparison between adjacent freshwater and terrestrial avian predators

Insight into processes determining the exposure of organohalogenated contaminants (OHCs) in wildlife might be gained from comparing predators in different ecosystems. This study compared two avian predator species with similar food chain lengths: the goldeneye duck (Bucephala clangula) and the tawny owl (Strix aluco) breeding in adjacent freshwater- and terrestrial ecosystems in central Norway. We measured lipophilic organochlorines (OCs) and protein-bound perfluorinated substances (PFASs) in eggs of the two species over 21 years (1999–2019). Across years, the proportional distribution of OCs (∼90% of the ΣOHC load) relative to PFASs (∼10%) was similar in the two species. Moreover, ΣOC concentrations were similar between the species, but PFAS compounds were 2–12 times higher in the goldeneyes than in tawny owls. OC-pesticides dominated in tawny owls (∼60% of ΣOC), whereas persistent polychlorinated biphenyl (PCBs) congeners were the main OC components in goldeneyes (∼70% of ΣOC). The lipid-normalized concentrations of most OC-pesticides and the less persistent PCB101 declined significantly in both species. Hexachlorobenzene (HCB), p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), and more persistent PCBs decreased in tawny owls, while they tended to increase in goldeneyes. The increase in HCB was particulary robust. Among the PFASs, contrasted temporal trends were found across the species for four out of 11 compounds: PFOS declined while most perfluorocarboxylic acids (PFCAs) increased in tawny owls. In contrast, most PFASs were stable in goldeneyes. Moreover, there was no annual covariance between the OHC exposure in the two species: i.e., high concentrations in one species in a given year did not translate into high concentrations in the other. Hence, the two avian predators in adjacent ecosystems seem to be subject to different processes determining the OHC exposure, probably related to variation in diet and climate, long-range transport of different contaminants, and emissions of pollution locally.

Evaluating the roles of biotransformation, spatial concentration differences, organism home range, and field sampling design on trophic magnification factors

Trophic magnification factors (TMFs) are field-based measurements of the bioaccumulation behavior of chemicals in food-webs. TMFs can provide valuable insights into the bioaccumulation behavior of chemicals. However, bioaccumulation metrics such as TMF may be subject to considerable uncertainty as a consequence of systematic bias and the influence of confounding variables. This study seeks to investigate the role of systematic bias resulting from spatially-variable concentrations in water and sediments and biotransformation rates on the determination of TMF. For this purpose, a multibox food-web bioaccumulation model was developed to account for spatial concentration differences and movement of organisms on chemical concentrations in aquatic biota and TMFs. Model calculated and reported field TMFs showed good agreement for persistent polychlorinated biphenyl (PCB) congeners and biotransformable phthalate esters (PEs) in a marine aquatic food-web. Model testing showed no systematic bias and good precision in the estimation of the TMF for PCB congeners but an apparent underestimation of model calculated TMFs, relative to reported field TMFs, for PEs. A model sensitivity analysis showed that sampling designs that ignore the presence of concentration gradients may cause systematically biased and misleading TMF values. The model demonstrates that field TMFs are most sensitive to concentration gradients and species migration patterns for substances that are subject to a low degree of biomagnification or trophic dilution. The model is useful in anticipating the effect of spatial concentration gradients on the determination of the TMF; guiding species collection strategies in TMF studies; and interpretation of the results of field bioaccumulation studies in study locations where spatial differences in chemical concentration exist.

Case–control study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women

BackgroundExposure to environmental chemicals may impair endocrine system function. Alaska Native (AN) women may be at higher risk of exposure to these endocrine disrupting chemicals, which may contribute to breast cancer in this population.ObjectiveTo measure the association between exposure to select environmental chemicals and breast cancer among AN women.DesignA case–control study of 170 women (75 cases, 95 controls) recruited from the AN Medical Center from 1999 to 2002. Participants provided urine and serum samples. Serum was analyzed for 9 persistent pesticides, 34 polychlorinated biphenyl (PCB) congeners, and 8 polybrominated diethyl ether (PBDE) congeners. Urine was analyzed for 10 phthalate metabolites. We calculated geometric means (GM) and compared cases and controls using logistic regression.ResultsSerum concentrations of most pesticides and 3 indicator PCB congeners (PCB-138/158; PCB-153, PCB-180) were lower in case women than controls. BDE-47 was significantly higher in case women (GM=38.8 ng/g lipid) than controls (GM=25.1 ng/g lipid) (p=0.04). Persistent pesticides, PCBs, and most phthalate metabolites were not associated with case status in univariate logistic regression. The odds of being a case were higher for those with urinary mono-(2-ethylhexyl) phthalate (MEHP) concentrations that were above the median; this relationship was seen in both univariate (OR 2.16, 95% CI 1.16–4.05, p=0.02) and multivariable (OR 2.43, 95% CI 1.13–5.25, p=0.02) logistic regression. Women with oestrogen receptor (ER)–/progesterone receptor (PR)-tumour types tended to have higher concentrations of persistent pesticides than did ER+/PR+ women, although these differences were not statistically significant.ConclusionsExposure to the parent compound of the phthalate metabolite MEHP may be associated with breast cancer. However, our study is limited by small sample size and an inability to control for the confounding effects of body mass index. The association between BDE-47 and breast cancer warrants further investigation.

Elucidating the structural properties that influence the persistence of PCBs in humans using the National Health and Nutrition Examination Survey (NHANES) dataset

In human exposure studies involving Polychlorinated Biphenyls (PCBs), it is useful to establish when an individual was potentially exposed. Age dating PCB exposure is complex but assessments can be made because different PCB congeners have different residence times in the human body. The less chlorinated congeners generally tend to have shorter residence times because they are biotransformed and eliminated faster than more chlorinated congeners. Therefore, the presence of high proportions of less chlorinated congeners is often indicative of recent exposure. The 2003–04 National Health and Nutrition Examination Survey (NHANES) dataset contains results for the concentration of 37 PCBs in a sub-sample of the US population. Multivariate statistical analysis of the NHANES data showed that less chlorinated congeners are not always biotransformed faster than higher chlorinated compounds. For example, PCB 28 (a tri-chlorobiphenyl) appears to be more resistant to biotransformation than PCB 101 and 110 (penta-chlorobiphenyls). Using statistical analysis of the NHANES data in conjunction with previously published studies on PCB persistence in humans, it was possible to identify the structural relationships that determine if a PCB is likely to be from a recent exposure (termed ‘episodic’) or from steady state exposure. Congeners with chlorine atoms in the 2,5- and 2,3,6-positions appear to be more susceptible to biotransformation whereas congeners with chlorine bonds in the 2,3,4- 2,4,5- 3,4,5- and 2,3,4,5-positions appear to be more persistent. This work shows that future investigations to date PCB exposure would benefit from the analysis of a wide range of congeners, including the selection of key congeners based not only on the degree of chlorination but also on the positions of the chlorine atoms on the biphenyl.

Persistent Organic Pollutants in Mediterranean Seawater and Processes Affecting Their Accumulation in Plankton

The Mediterranean and Black Seas are unique marine environments subject to important anthropogenic pressures due to riverine and atmospheric inputs of organic pollutants. Here, we report the results obtained during two east-west sampling cruises in June 2006 and May 2007 from Barcelona to Istanbul and Alexandria, respectively, where water and plankton samples were collected simultaneously. Both matrixes were analyzed for hexaclorochyclohexanes (HCHs), hexachlorobenzene (HCB), and 41 polychlorinated biphenyl (PCB) congeners. The comparison of the measured HCB and HCHs concentrations with previously reported dissolved phase concentrations suggests a temporal decline in their concentrations since the 1990s. On the contrary, PCB seawater concentrations did not exhibit such a decline, but show a significant spatial variability in dissolved concentrations with lower levels in the open Western and South Eastern Mediterranean, and higher concentrations in the Black, Marmara, and Aegean Seas and Sicilian Strait. PCB and OCPs (organochlorine pesticides) concentrations in plankton were higher at lower plankton biomass, but the intensity of this trend depended on the compound hydrophobicity (K(OW)). For the more persistent PCBs and HCB, the observed dependence of POP concentrations in plankton versus biomass can be explained by interactions between air-water exchange, particle settling, and/or bioaccumulation processes, whereas degradation processes occurring in the photic zone drive the trends shown by the more labile HCHs. The results presented here provide clear evidence of the important physical and biogeochemical controls on POP occurrence in the marine environment.

A pilot study of pesticides and PCBs in the breast milk of women residing in urban and agricultural communities of California

Currently, there is no nationally representative human milk biomonitoring program in the United States (U.S.) and no studies have reported non-persistent pesticides in the milk of U.S. women. In this pilot study we developed a multiresidue laboratory method to measure non-persistent and persistent pesticides and polychlorinated biphenyl (PCB) congeners in human milk samples from women residing in the agricultural region of Salinas, CA (n = 13) and the urban San Francisco Bay Area, CA (n = 21). Samples were collected from 2002-2007. Median concentrations in pg g(-1) milk among urban and agricultural women, respectively were reported for: chlorpyrifos (24.5 and 28.0), cis-permethrin (81.9 and 103), trans-permethrin (93.1 and 176), hexachlorobenzene (191 and 223), β-hexachlorocyclohexane (220 and 443), o,p'-DDT (36.6 and 62.4), p,p'-DDT,(107 and 102), o,p'-DDE (5.65 and 5.17), p,p'-DDE (3170 and 3490), dacthal (2.79 and 3.43), PCB 118 (92.8 and 17.0), PCB 138 (183 and 38.2), PCB 153 (242 and 43.6) and PCB 180 (239 and 683). Among urban women, median concentrations were 4.02 and 4.32 pg g(-1) milk for chlorpyrifos-methyl and propoxur, respectively. These results suggest that neonates and young children may be exposed to persistent and non-persistent pesticides and PCBs via breast milk.

Contribution of Fecal Egestion to the Whole Body Elimination of Polychlorinated Biphenyls by Japanese Koi (Cyprinus carpio)

This research investigated dose-dependent whole body and fecal elimination of 39 polychlorinated biphenyl (PCB) congeners spanning a range of chemical hydrophobicities (log Kow) by the Japanese koi (Cyprinus carpio). Both whole body (ktot) and fecal (keg) PCB congener elimination rate coefficients were negatively correlated with log Kow and observed to be dose independent. PCB congener ktot values determined for koi were representative of those generated for fish species of similar size and reared at near optimal temperatures. For persistent and metabolized-type PCB congeners, no significant difference was observed between the regressions describing the relationships between ktot and log Kow for these congeners. Individual PCB congener keg coefficient estimates ranged between 1% and 20% of their respective ktot values but averaged only 5% of the magnitude of ktot over a log Kow range of 5.7-7.8. These results verify first-order kinetics of PCB elimination by a fish species and demonstrate that the relative contribution of keg to ktot is negligible, even for highly hydrophobic (log Kow>6.5) compounds. It was concluded that gill elimination is the primary mechanism of elimination for persistent organic pollutants such as PCBs by Japanese koi.

PERSISTENT OR NOT PERSISTENT? POLYCHLORINATED BIPHENYLS ARE READILY DEPURATED BY GRIZZLY BEARS (URSUS ARCTOS HORRIBILIS)

Major pharmacokinetic processes influencing polychlorinated biphenyl (PCB) accumulation in mammals include uptake, biotransformation, respiration, and excretion. We characterized some of the factors underlying PCB accumulation/loss by evaluating PCB concentrations and patterns in pre- and posthibernation grizzly bears (Ursus arctos horribilis) and their prey. The PCB congeners with vicinal meta- and para-chlorine unsubstituted hydrogen positions consistently showed loss both before and during hibernation, supporting the idea of a dominant role for biotransformation. Retention of all other studied congeners relative to that of PCB 194 varied widely (from <1 to 100%) and was highly correlated with log octanol-water partition coefficient (p < 0.0001). A lack of loss for most of these other congeners during hibernation supports the notion that excretion (e.g., fecal or urinary) or lack of uptake during the feeding season underlies their lack of accumulation, because hibernating bears do not eat or excrete. We estimate that grizzly bears retain less than 10% of total PCBs taken up from their diet. Our results suggest that for grizzly bears, depuration of PCBs via biotransformation is important (explaining approximately 40% of loss), but that nonbiotransformation processes, such as excretion, may be more important (explaining approximately 60% of loss). These findings, together with the approximately 91% loss of the persistent PCB 153 congener relative to PCB 194 in grizzly bears, raise important questions about how one defines persistence of PCBs in wildlife and may have bearing on the interpretation of food-web biomagnification studies.

Bioaccumulation and biotransformation of 61 polychlorinated biphenyl and four polybrominated diphenyl ether congeners in juvenile American kestrels (Falco sparverius)

This study examined the bioaccumulation and dietary retention of 61 polychlorinated biphenyl (PCB) and four polybrominated diphenyl ether (PBDE) congeners in juvenile American kestrels (Falco sparverius). American kestrels were exposed to contaminants via egg injection and daily gavage dosing over the posthatch-to-fledgling period. Retention factors for PCBs were dependent on chemical hydrophobicity and chlorine substitution patterns and ranged from less than 1 to 16.4% for PCBs having vicinal hydrogen substitutions at meta-, para- carbons on at least one of the phenyl rings and between 13.2 and 81.5% for congeners containing chlorine substitutions at 4,4'-, 3',4,5'-, 3,4',5-, or 3,3',5,5'-positions. These results indicate that juveniles are capable of biotransforming PCBs according to the same structure-activity rules as adults. A toxicokinetic model, initially parameterized using adult toxicokinetic parameters, was used to describe concentration trends in juveniles over time. The adult model overestimated PCB concentrations but provided an adequate fit when elimination rate constants were increased by a factor of 12.7. Retention factors for the PBDE congeners 2,2',4,4'-tetrabromodiphenyl ether (BDE 47), 2,2',4,4',6-pentabromodiphenyl ether (BDE 100), 2,2',4,4',5-pentabromodiphenyl ether (BDE 99), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE 153) were from 7.8 to 45.3% of the total dose. The retention of BDE 47 was similar that observed for readily cleared PCBs, whereas the remaining PBDEs exhibited retention factors consistent with those of persistent PCBs. Half-lives for PBDEs in juveniles were estimated to range from 5.6 to 44.7 d. Assuming differences in PBDE toxicokinetics between juveniles and adults similar to those measured for PCBs, adult American kestrel PBDE half-lives are expected to range from 72 to 572 d.

PCB Elimination by Yellow Perch (Perca flavescens) during an Annual Temperature Cycle

The significance of temperature on aquatic species ecology and physiology is well recognized yet its effects on chemical bioaccumulation kinetics are less well understood under natural conditions. In this study, yellow perch were dosed with a polychlorinated biphenyl (PCB) mixture and allowed to depurate the chemicals over 1 year under an ambient temperature cycle characteristic of northern temperate latitudes. PCB elimination kinetics during the summer months at optimal water temperature for perch (23 degrees C) were similar to those observed in lab studies with other species reared at their optimal temperature. During the fall and winter seasons, however, elimination of only 11 PCB congeners of log K(ow) < or = 5.7 was observed and half-lives averaged > 1000 d for these PCBs. PCB elimination was again observed with the onset of spring temperatures but elimination rates averaged 2.6 times slower for readily metabolized congeners and 7.5 times slower for more persistent PCBs than observed during the summer. Bioenergetics modeling efforts predicted maximum values for respiration, fecal egestion, and growth rates during summer months but also predicted rapid declines in these chemical dilution processes during the fall and winter concurrent with changes in temperature. As temperature increased into the spring, bioenergetic rates were predicted to increase but only achieved approximately 85% of maximum rates predicted for summer peak temperatures. These results indicate that minimal chemical elimination occurs in perch when metabolic functioning falls to low maintenance levels during the fall and winter. These seasons encompass approximately 8 months of the year at northern temperate latitudes and therefore these patterns have significant consequences for understanding mechanisms of food-web biomagnification of hydrophobic organic chemicals in aquatic systems.

Characterization of the PCB Substrate Range of Microbial Dechlorination Process LP

We have characterized the substrate range of Process LP, a PCB dechlorination activity mediated by anaerobic bacteria, in Housatonic River sediment (Lenox, MA). Process LP has the rare ability to remove unflanked para chlorines from polychlorinated biphenyls (PCBs). We used 2,6-difluoro-4-chlorobiphenyl (DFCB) to activate Process LP in anoxic sediment microcosms and tested its ability to dechlorinate 34 potential PCB substrates, all of which are significant components of PCB mixtures found in contaminated sediments. We used gas chromatography-mass spectrometry to monitor the dechlorination of DFCB and PCBs and the appearance of products. The preferred substrates for Process LP were PCB congeners in which the target para chlorines were flanked by meta chlorines, such as those having 3,4- and 2,4,5-chlorophenyl rings. The unflanked para chlorines on PCBs with 2,4-, 2,4,6-, and sometimes 4-chlorophenyl rings, were also substrates. Furthermore, the data revealed that Process LP can also meta-dechlorinate 2,3-, 2,3,4-, and 2,3,5-chlorophenyl groups on some congeners. A single ortho chlorine on the unattacked ring generally enhanced dechlorination activity, but the presence of 3 or 4 ortho chlorines or a 4-chlorophenyl group decreased the dechlorination efficiency. PCBs with 2,4-, 2,4,6-, 2,3-, and 2,3,5-chlorophenyl rings are often terminal dechlorination products of other microbial dechlorination activities. Since these PCBs are substrates for Process LP, this dechlorination activity works especially well in tandem with other dechlorination activities and further reduces the toxicity and persistence of PCBs. The data presented here will facilitate the construction of accurate models to interpret in situ PCB dechlorination and predict PCB fate.

The relationship between levels of PCBs and pesticides in human hair and blood: preliminary result.

Human hair as a biologic measure of exposure to persistent organic pollutants (POPs) has some advantages over the more commonly used blood and adipose tissue samples. However, one of the primary limitations is the difficulty in distinguishing between exogenous and endogenous contamination. In addition, there are currently no standardized methods for hair sample collection, washing, and chemical analysis. There is also very limited information describing the correlation between levels of organic contaminants in hair and other body compartments. To explore levels of POPs in blood and hair, samples from 10 volunteers were collected and analyzed for select organochlorine pesticides and 57 individual polychlorinated biphenyl (PCB) congeners. We demonstrated that the method for analyzing organic contaminants in human hair was reliable and reproducible. Washing hair with shampoo decreased levels of PCBs, pesticides, and lipids by 25–33% on average and up to 62% for low-chlorinated congeners. The percentage of lipids and the levels of organochlorines in hair were higher than in serum. We found strong correlation (r = 0.8) between p,p′-DDE (dichlorodiphenyldichloroethylene) levels in hair and blood and moderate correlations for the more persistent PCB congeners, but no correlations or weak correlations for other organochlorines. The present study provides preliminary evidence on the utility of hair analysis for POPs; however, further larger studies are recommended before hair analysis can be successfully applied in epidemiologic studies on POPs.

Enantiomeric signatures of chiral polychlorinated biphenyl atropisomers in livers of harbour porpoises (Phocoena phocoena) from the southern North Sea.

The enantiomeric composition of polychlorinated biphenyl (PCB) atropisomers, including PCB 95, PCB 149 and PCB 132, was measured in 11 livers of harbour porpoises (Phocoena phocoena) from the southern North Sea. Non-racemic enantiomeric ratios (ERs) were found in some samples. The value of ERs in three of the four juvenile porpoises was equal or almost equal to one, while the ERs in all adults differed from racemic and ranged from 1.31 to 2.54 for PCB 95; from 1.19 to 1.81 for PCB 149 and from 0.45 to 0.94 for PCB 132. There were no relationships between the total concentration of PCBs and ERs. To understand the phenomena, the relationships between the ER value of individual chiral congener with age, concentration of total PCBs and PCB congener pattern were discussed. A model of intake and elimination kinetics was set up and it was tested using the ratio between concentration of PCB 153 and PCB 101 in the liver samples. There was a clear trend between the enantiomeric ratios and the ratio between PCB 153 and PCB 101. Considering that PCB 153 is one of the most persistent PCB congeners in marine mammals and PCB 101 is a relatively easy metabolised congener, this trend means that the enantiomeric ratio most likely reflects the proportion of the metabolised congener. The exposure period in contaminated conditions has a strong impact on ERs, and it is suggested that ERs in wildlife, combined with information on their anthropometric data, health status, diet and habitat conditions, might be good indicators of pollution in coastal ecosystems.

Continuous surveillance of organochlorine compounds in human breast milk from 1972 to 1998 in Osaka, Japan.

The presence of chlorinated organic compounds in breast milk of lactating women living in Osaka Prefecture, Japan, has been followed since 1972. Following the highest concentration found at the start of the measurements, contamination by polychlorinated biphenyls (PCBs) and organochlorine pesticides, such as beta-HCH and DDT declined to about 3-13% of the peak levels by the mid-1970s and continued to decrease to low-level equilibrium states. This decline varies greatly with the chemical compound. In comparison with 1970s, when the contamination of breast milk was highest, the beta-HCH level fell to about 3%, DDT to about 7%, and PCBs to about 13%, representative of different half-lives in the environment and the particular persistence of PCB. In the case of chlordane, a termite insecticide, more than 10 years have passed since its use was prohibited in Japan, but it continues to be found in human breast milk, although at a low level.

Prenatal PCB exposure and neonatal behavioral assessment scale (NBAS) performance

We examined the relationship between prenatal (cord blood) polychlorinated biphenyls (PCBs) and Neonatal Behavioral Assessment Scale (NBAS) performance in babies born to women who consumed contaminated Lake Ontario fish. Cord blood PCBs, DDE, HCB, Mirex, lead, and hair mercury levels were determined for 152 women who reported never consuming Lake Ontario fish and 141 women who reported consuming at least 40 PCB-equivalent lbs. of Lake Ontario fish over their lifetime. Earlier work demonstrated that the newborns of fish eaters are exposed to a more heavily chlorinated distribution of PCB congeners, and that highly chlorinated PCBs (hepta-, octa-, and nonachlorinated biphenyls) are most strongly correlated with breast milk levels, perhaps providing the best index of PCB exposure in the Oswego cohort. Given the above, one would predict that these PCBs would be related to impaired performance on those NBAS clusters associated with fish consumption; namely Habituation, Autonomic, and Reflex clusters of the NBAS. Excepting the Relex cluster, these predictions were confirmed. Results revealed significant linear relationships between the most heavily chlorinated PCBs and performance impairments on the Habituation and Autonomic clusters of the NBAS at 25–48 h after birth. Additionally, higher prenatal PCB exposure was associated with a nonspecific performance impairment on the NBAS as evidenced by a significantly greater proportion of NBAS scales in which poor performance was exhibited (more than 1 standard deviation below the mean) in the most highly exposed neonates. Moreover, PCBs of lighter chlorination were unrelated to NBAS performance, as were DDE, Mirex, HCB, lead, and mercury. These results corroborate our earlier findings linking Lake Ontario fish consumption to the most heavily chlorinated PCB congeners, and suggest that the chlorination and persistence of PCBs may be an important factor both for exposure assessment and for determining relationships with neurobehavioral functions.

Polychlorinated biphenyls induce meiotic length mutations at the human minisatellite MS32 in yeast

Polychlorinated biphenyls (PCBs) are lipophilic compounds, several of which are toxic and carcinogenic. Complex mixtures of PCBs (e.g., Aroclor) have been widely used in the industry. The persistence of PCBs, in combination with poor waste management, has led to a large-scale distribution of PCBs in the biosphere. The toxic and carcinogenic effects of PCBs are poorly understood, but are suggested to be associated with Ah receptor binding and induction of the Ah-gene battery. We have previously shown that a higher-chlorinated PCB mixture, Aroclor 1254, significantly increased the germline mutation rate at the mouse minisatellite PC-1. We have recently developed an in vitro model system to study and characterize spontaneous and induced meiotic mutations in human minisatellites integrated in yeast. Here, for the first time, we have used this model system to show that chemicals, in this case Aroclor 1254, can induce meiotic length mutations at the human minisatellite MS32 in a yeast strain harboring 38- and 42-repeat-unit alleles. The results also show that the size distribution of mutant MS32 alleles differs between PCB and the control, with a larger proportion of mutant allele sizes below 29 repeat units in the PCB series. These alleles were not structurally different from the alleles of the same size in the control. We conclude that PCBs induce minisatellite mutations in meiosis and have recombinogenic properties, and that the mutations are induced in an Ah receptor-independent manner. The induction of minisatellite mutations in meiosis as an indication of genomic damage must be taken into account in the risk assessment of PCBs and other environmental contaminants.

Interactions between Methylsulfonyl PCBs and the Glucocorticoid Receptor

Persistent polychlorinated biphenyl (PCB) metabolites were studied with respect to their interaction with the human glucocorticoid receptor (GR). 3-Methylsulphonyl-2,5,6,2',4',5'-hexachlorobiphenyl (3-MeSO2-CB149) was shown to compete with 3H-dexamethasone for binding to the GR, with an IC50 (concentration that inhibits 50%) of approximately 1 microM. Using GRAF cells expressing human GR, glucocorticoid responsive element, and a reporter enzyme, we demonstrated that 3-MeSO2-CB149 functionally acts as an antagonist at the GR (IC50 = 2.7 microM). In accordance with the receptor binding, the antagonism mainly appeared to be of a competitive nature. When studying the competitive binding of 24 methylsulfonyl PCBs (relative to dexamethasone) to GR from mouse liver cytosol, seven compounds had a higher affinity to GR than 3-MeSO2-CB149. Structure-activity relationship studies indicated that the presence of three chlorine atoms in the ortho-position and chlorine and methyl sulfone groups on either end of the molecule (4 and 4'-position) increased the affinity to GR. The relevance of this finding for human health is not known, but PCB methyl sulfones are ubiquitous pollutants present in mother's milk. The results stress the need for studying endocrine disruptors that affect hormonal systems other than sex and thyroidogenic hormones.

Interactions between methylsulfonyl PCBs and the glucocorticoid receptor.

Persistent polychlorinated biphenyl (PCB) metabolites were studied with respect to their interaction with the human glucocorticoid receptor (GR). 3-Methylsulphonyl-2,5,6,2',4',5'-hexachlorobiphenyl (3-MeSO2-CB149) was shown to compete with 3H-dexamethasone for binding to the GR, with an IC50 (concentration that inhibits 50%) of approximately 1 microM. Using GRAF cells expressing human GR, glucocorticoid responsive element, and a reporter enzyme, we demonstrated that 3-MeSO2-CB149 functionally acts as an antagonist at the GR (IC50 = 2.7 microM). In accordance with the receptor binding, the antagonism mainly appeared to be of a competitive nature. When studying the competitive binding of 24 methylsulfonyl PCBs (relative to dexamethasone) to GR from mouse liver cytosol, seven compounds had a higher affinity to GR than 3-MeSO2-CB149. Structure-activity relationship studies indicated that the presence of three chlorine atoms in the ortho-position and chlorine and methyl sulfone groups on either end of the molecule (4 and 4'-position) increased the affinity to GR. The relevance of this finding for human health is not known, but PCB methyl sulfones are ubiquitous pollutants present in mother's milk. The results stress the need for studying endocrine disruptors that affect hormonal systems other than sex and thyroidogenic hormones.

Alterations in Rat Brain Thyroid Hormone Status Following Pre- and Postnatal Exposure to Polychlorinated Biphenyls (Aroclor 1254)

The effects of daily oral maternal exposure to 0, 5, or 25 mg/kg body wt of a polychlorinated biphenyl (PCB) mixture (Aroclor 1254) on Days 10 to 16 of gestation on plasma and brain thyroid hormone concentrations and peripheral thyroid hormone metabolism were examined in fetal and weanling rats. Plasma thyroid hormone levels and hepatic microsomal thyroid hormone glucuronidation were also examined in pregnant rats and the adult offspring. Plasma and brain levels of PCBs and hydroxylated PCB metabolites were analyzed in fetal, weanling, and adult offspring. Maternal exposure to Aroclor 1254 significantly decreased fetal (Gestation Day 20) and neonatal (Postnatal Day 4) plasma total thyroxine (T4) and free T4levels in a dose-dependent manner. Effects of maternal Aroclor 1254 exposure on plasma total and free T4concentrations were less pronounced in offspring at 21 days of age and absent 90 days after birth. Plasma concentrations of thyroid-stimulating hormone were unaltered in fetuses, neonates, weanling rats, and adult offspring following maternal treatment with Aroclor 1254. The concentration of T4was severely depressed in the forebrain and cerebellum of fetal rats on Day 20 of gestation following maternal Aroclor 1254 exposure. Brain triiodothyronine (T3) concentrations in the Aroclor-exposed fetuses were significantly decreased relative to control values only in the low-dose group. On Day 21 postpartum T4concentrations were significantly decreased in the forebrains of female weanling rats from the 25 mg Aroclor 1254/kg dose group, and no reductions were observed in forebrain T3concentrations in male or female neonates. The deiodination of T4to T3was significantly increased in fetal forebrain homogenates by both PCB treatments. In female weanling brain homogenates the deiodination of T4to T3was significantly decreased in the low-dose group and unaltered in the high-dose group. No alterations in brain thyroid hormone metabolism were observed in forebrain homogenates from adult offspring exposed pre- and postnatally to Aroclor 1254. Hepatic microsomal T4glucuronidation was significantly decreased in fetal microsomes following perinatal PCB exposure and significantly increased in weanling hepatic microsomes in a dose-dependent manner. An accumulation of mainly one PCB metabolite, 2,3,3′,4′,5-pentachloro-4-biphenylol was observed in fetal plasma and forebrain on Gestation Day 20 and in neonatal and weanling rat plasma on Postnatal Days 4, 21, and 90. The plasma level of 2,3,3′,4′,5-pentachloro-4-biphenylol was higher than that of the persistent PCB congener 2,2′,4,4′,5,5′-hexachlorobiphenyl in the control and PCB-exposed offspring up to Postnatal Day 21, and even after 90 days, the 2,3,3′,4′,5-pentachloro-4-biphenylol was present in amounts approximately equal to those of CB 153. Although PCB levels were relatively high in the weanling rat forebrain, no hydroxylated PCB metabolites were detected. On Day 90 postpartum, plasma levels of PCBs and 2,3,3′,4′,5-pentachloro-4-biphenylol were still elevated in the offspring of PCB-treated dams relative to controls. These results suggest that the accumulation of hydroxylated PCB metabolites in fetal plasma can reduce fetal plasma T4levels and accordingly fetal brain T4levels. However, in late gestational fetuses, the induction of brain type II thyroxine 5′-deiodinase activity compensates for decreases in brain T4levels, so that brain T3levels are maintained.