Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment.

Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Québec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies

Serum and follicular fluid organochlorine concentrations among women undergoing assisted reproduction technologies

<p>Abstract</p> <p>Background</p> <p>Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error.</p> <p>Methods</p> <p>The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(<it>p</it>-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women.</p> <p>Results</p> <p>Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid:serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentrations between samples collected between years 1994–1998 and those collected in 1999–2003.</p> <p>Conclusion</p> <p>Our results support the use of a single serum sample to adequately represent a more biologically relevant dose (concentrations in follicular fluid), as well as exposure levels over time, in epidemiological studies of ART outcomes in relation to organochlorine exposure.</p

Evaluation of the Webler-Brown model for estimating tetrachloroethylene exposure from vinyl-lined asbestos-cement pipes

<p>Abstract</p> <p>Background</p> <p>From May 1968 through March 1980, vinyl-lined asbestos-cement (VL/AC) water distribution pipes were installed in New England to avoid taste and odor problems associated with asbestos-cement pipes. The vinyl resin was applied to the inner pipe surface in a solution of tetrachloroethylene (perchloroethylene, PCE). Substantial amounts of PCE remained in the liner and subsequently leached into public drinking water supplies.</p> <p>Methods</p> <p>Once aware of the leaching problem and prior to remediation (April-November 1980), Massachusetts regulators collected drinking water samples from VL/AC pipes to determine the extent and severity of the PCE contamination. This study compares newly obtained historical records of PCE concentrations in water samples (n = 88) with concentrations estimated using an exposure model employed in epidemiologic studies on the cancer risk associated with PCE-contaminated drinking water. The exposure model was developed by Webler and Brown to estimate the mass of PCE delivered to subjects' residences.</p> <p>Results</p> <p>The mean and median measured PCE concentrations in the water samples were 66 and 0.5 μg/L, respectively, and the range extended from non-detectable to 2432 μg/L. The model-generated concentration estimates and water sample concentrations were moderately correlated (Spearman rank correlation coefficient = 0.48, p < 0.0001). Correlations were higher in samples taken at taps and spigots vs. hydrants (ρ = 0.84 vs. 0.34), in areas with simple vs. complex geometry (ρ = 0.51 vs. 0.38), and near pipes installed in 1973–1976 vs. other years (ρ = 0.56 vs. 0.42 for 1968–1972 and 0.37 for 1977–1980). Overall, 24% of the variance in measured PCE concentrations was explained by the model-generated concentration estimates (p < 0.0001). Almost half of the water samples had undetectable concentrations of PCE. Undetectable levels were more common in areas with the earliest installed VL/AC pipes, at the beginning and middle of VL/AC pipes, at hydrants, and in complex pipe configurations.</p> <p>Conclusion</p> <p>PCE concentration estimates generated using the Webler-Brown model were moderately correlated with measured water concentrations. The present analysis suggests that the exposure assessment process used in prior epidemiological studies could be improved with more accurate characterization of water flow. This study illustrates one method of validating an exposure model in an epidemiological study when historical measurements are not available.</p

In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Background The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. Methodology/Principal Findings We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. Conclusions/Significance Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Educatio