Development of urine standard reference materials for metabolites of organic chemicals including polycyclic aromatic hydrocarbons, phthalates, phenols, parabens, and volatile organic compounds.

Two new Standard Reference Materials (SRMs), SRM 3672 Organic Contaminants in Smokers' Urine (Frozen) and SRM 3673 Organic Contaminants in Non-Smokers' Urine (Frozen), have been developed in support of studies for assessment of human exposure to select organic environmental contaminants. Collaborations among three organizations resulted in certified values for 11 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and reference values for 11 phthalate metabolites, 8 environmental phenols and parabens, and 24 volatile organic compound (VOC) metabolites. Reference values are also available for creatinine and the free forms of caffeine, theobromine, ibuprofen, nicotine, cotinine, and 3-hydroxycotinine. These are the first urine Certified Reference Materials characterized for metabolites of organic environmental contaminants. Noteworthy, the mass fractions of the environmental organic contaminants in the two SRMs are within the ranges reported in population survey studies such as the National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS). These SRMs will be useful as quality control samples for ensuring compatibility of results among population survey studies and will fill a void to assess the accuracy of analytical methods used in studies monitoring human exposure to these organic environmental contaminants.

Milk and serum standard reference materials for monitoring organic contaminants in human samples.

Four new Standard Reference Materials (SRMs) have been developed to assist in the quality assurance of chemical contaminant measurements required for human biomonitoring studies, SRM 1953 Organic Contaminants in Non-Fortified Human Milk, SRM 1954 Organic Contaminants in Fortified Human Milk, SRM 1957 Organic Contaminants in Non-Fortified Human Serum, and SRM 1958 Organic Contaminants in Fortified Human Serum. These materials were developed as part of a collaboration between the National Institute of Standards and Technology (NIST) and the Centers for Disease Control and Prevention (CDC) with both agencies contributing data used in the certification of mass fraction values for a wide range of organic contaminants including polychlorinated biphenyl (PCB) congeners, chlorinated pesticides, polybrominated diphenyl ether (PBDE) congeners, and polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) congeners. The certified mass fractions of the organic contaminants in unfortified samples, SRM 1953 and SRM 1957, ranged from 12 ng/kg to 2200 ng/kg with the exception of 4,4'-DDE in SRM 1953 at 7400 ng/kg with expanded uncertainties generally <14 %. This agreement suggests that there were no significant biases existing among the multiple methods used for analysis.

Bisphenol A is not detectable in media or selected contact materials used in IVF.

There is a lack of data regarding potential exposure of gametes to bisphenol A during IVF. Detectable concentrations of bisphenol A were not found in commonly used IVF plastic culture dishes, suction tubing or growth media under normal-use conditions.

Dioxin and polychlorinated biphenyl concentrations in mother's serum and the timing of pubertal onset in sons.

BACKGROUND: Animal studies have demonstrated that timing of pubertal onset can be altered by prenatal exposure to dioxins or polychlorinated biphenyls (PCBs), but studies of human populations have been quite limited. METHODS: We assessed the association between maternal serum concentrations of dioxins and PCBs and the sons' age of pubertal onset in a prospective cohort of 489 mother-son pairs from Chapaevsk, Russia, a town contaminated with these chemicals during past industrial activity. The boys were recruited at ages 8 to 9 years, and 4 years of annual follow-up data were included in the analysis. Serum samples were collected at enrollment from both mothers and sons for measurement of dioxin and PCB concentrations using high-resolution mass spectrometry. The sons' pubertal onset--defined as pubertal stage 2 or higher for genitalia (G) or pubic hair (P), or testicular volume >3 mL--was assessed annually by the same physician. RESULTS: In multivariate Cox models, elevated maternal serum PCBs were associated with earlier pubertal onset defined by stage G2 or higher (4th quartile hazard ratio = 1.7 [95% confidence interval = 1.1- 2.5]), but not for stage P2 or higher or for testicular volume >3 mL. Maternal serum concentrations of dioxin toxic equivalents were not consistently associated with the sons' pubertal onset, although a dose-related delay in pubertal onset (only for G2 or higher) was seen among boys who breast-fed for 6 months or more. CONCLUSIONS: Maternal PCB serum concentrations measured 8 or 9 years after sons' births--which may reflect sons' prenatal and early-life exposures--were associated with acceleration in some, but not all, measures of pubertal onset.

Partition of environmental chemicals between maternal and fetal blood and tissues.

Passage of environmental chemicals across the placenta has important toxicological consequences, as well as for choosing samples for analysis and for interpreting the results. To obtain systematic data, we collected in 2000 maternal and cord blood, cord tissue, placenta, and milk in connection with births in the Faroe Islands, where exposures to marine contaminants is increased. In 15 sample sets, we measured a total of 87 environmental chemicals, almost all of which were detected both in maternal and fetal tissues. The maternal serum lipid-based concentrations of organohalogen compounds averaged 1.7 times those of cord serum, 2.8 times those of cord tissue and placenta, and 0.7 those of milk. For organohalogen compounds detectable in all matrices, a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed (r(2) > 0.5). Greater degree of chlorination resulted in lower transfer from maternal serum into milk. Concentrations of pentachlorbenzene, γ-hexachlorocyclohexane, and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels. Perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum. Cadmium, lead, mercury, and selenium were all detected in fetal samples, but only mercury showed close correlations among concentrations in different matrices. Although the environmental chemicals examined pass through the placenta and are excreted into milk, partitions between maternal and fetal samples are not uniform.

Estimation of background serum 2,3,7,8-TCDD concentrations by using quantile regression in the UMDES and NHANES populations.

BACKGROUND: The goal of the present study was to quantify the population-based background serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by using data from the reference population of the 2005 University of Michigan Dioxin Exposure Study (UMDES) and the 2003-2004 National Health and Nutrition Examination Survey (NHANES). METHODS: Multiple imputation was used to impute the serum TCDD concentrations below the limit of detection by combining the 2 data sources. The background mean, quartiles, and 95th percentile serum TCDD concentrations were estimated by age and sex by using linear and quantile regressions for complex survey data. RESULTS: Any age- and sex-specific mean, quartiles, and 95th percentiles of background serum TCDD concentrations of study participants between ages 18 and 85 years can be estimated from the regressions for the UMDES reference population and the NHANES non-Hispanic white population. For example, for a 50-year-old man in the reference population of UMDES, the mean, quartiles, and 95th percentile serum TCDD concentrations are estimated to be 1.1, 0.6, 1.1, 1.8, and 3.3 parts per trillion, respectively. The study also shows that the UMDES reference population is a valid reference population for serum TCDD concentrations for other predominantly white populations in Michigan. CONCLUSION: The serum TCDD concentrations increased with age and increased more over age in women than in men, and hence estimation of background concentrations must be adjusted for age and sex. The methods and results discussed in this article have wide application in studies of the concentrations of chemicals in human serum and in environmental samples.

A Pilot Study Evaluating Organochlorine and Organophosphate Pesticide Exposure in Children and Adolescents of Mexican Descent Residing in Hidalgo County, Texas.

Children and adolescents of Mexican descent residing in Hidalgo County (TX) were evaluated for exposure to organochlorine (OC) and organophosphate (OP) pesticides. A convenience sample of 60 participants enrolled in our pilot study. The lipid-adjusted serum concentrations of nine OC metabolites and creatinine-adjusted urinary concentrations of six OP metabolites were measured and compared with data from the Centers for Disease Control and Prevention's Fourth Report on Human Exposure to Environmental Chemicals. Descriptive statistics were used to summarize the concentration levels for each metabolite. Study participants were aged 5-18 years. For most of the OC and OP metabolites, our findings showed that participants had concentration levels within the distributional range of the national data. However, notable outlying levels (greater than the 95th percentile in the Fourth Report) were identified for the following OC metabolites: gamma-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethene, and p,p'-dichlorodiphenyltrichloroethane. Among the children aged 5-11 years, one child had an outlying value for the OP metabolite: dimethylphosphate. Our findings on the levels of OC and OP pesticide exposure enhances the credibility of national estimates, and can serve as baselines for children and adolescents of Mexican descent residing in Lower Rio Grande Valley. Furthermore, our study contributes to the lacunae of knowledge regarding environmental exposures and presses further investigation of outlying OC and OP exposure levels.

Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin.

BACKGROUND: Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy. METHODS AND FINDINGS: Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i) a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination), and 1,772 age-matched women from the surrounding noncontaminated area (reference); (ii) a biomarker study on 51 mother-child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH) was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 microU/ml (95% confidence interval [CI] 0.90-1.08) in the reference area (n = 533), 1.35 microU/ml (95% CI 1.22-1.49) in zone B (n = 425), and 1.66 microU/ml (95% CI 1.19-2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b-TSH > 5 microU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001). Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, beta = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, beta = 0.45, p = 0.005). CONCLUSIONS: Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.

Birth delivery mode modifies the associations between prenatal polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels.

BACKGROUND: Developing infants may be especially sensitive to hormone disruption from chemicals including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). OBJECTIVE: We investigated relationships between cord serum levels of PCBs and PBDEs and thyroid hormones measured in cord blood serum and neonatal blood spots. METHODS: We measured PCBs and PBDEs, thyrotropin (TSH), thyroxine (T4) and free T4 (FT4) in cord blood serum from 297 infants who were delivered at the Johns Hopkins Hospital in 2004-2005. We abstracted results of total T4 (TT4) measured in blood spots collected in the hospital and at neonatal visits. We used delivery mode (augmented vaginal deliveries and nonelective cesarean deliveries) as a surrogate for intrapartum stress, which is known to alter cord blood thyroid hormones. RESULTS: In the full study population, no compounds were associated with a change in average TSH, FT4, or TT4. BDE-100 was associated with increased odds of low cord TT4, BDE-153 with increased odds of low cord TT4 and FT4, and no compounds were associated with increased odds of high TSH. For infants born by spontaneous, vaginal, unassisted deliveries, PCBs were associated with lower cord TT4 and FT4 and lower TT4 measured in neonatal blood spots. PBDEs showed consistent but mainly nonsignificant negative associations with TT4 and FT4 measurements. CONCLUSIONS: Prenatal PCB and PBDE exposures were associated with reduced TT4 and FT4 levels among infants born by spontaneous, unassisted vaginal delivery. Intrapartum stress associated with delivery mode may mask hormonal effects of PCBs and PBDEs.

Dioxin exposure, from infancy through puberty, produces endocrine disruption and affects human semen quality.

BACKGROUND: Environmental toxicants are allegedly involved in decreasing semen quality in recent decades; however, definitive proof is not yet available. In 1976 an accident exposed residents in Seveso, Italy, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). OBJECTIVE: The purpose of this study was to investigate reproductive hormones and sperm quality in exposed males. METHODS: We studied 135 males exposed to TCDD at three age groups, infancy/prepuberty (1-9 years), puberty (10-17 years), and adulthood (18-26 years), and 184 healthy male comparisons using 1976 serum TCDD levels and semen quality and reproductive hormones from samples collected 22 years later. RESULTS: Relative to comparisons, 71 men (mean age at exposure, 6.2 years; median serum TCDD, 210 ppt) at 22-31 years of age showed reductions in sperm concentration (53.6 vs. 72.5 million/mL; p = 0.025); percent progressive motility (33.2% vs. 40.8%; p < 0.001); total motile sperm count (44.2 vs. 77.5 x 10(6); p = 0.018); estradiol (76.2 vs. 95.9 pmol/L; p = 0.001); and an increase in follicle-stimulating hormone (FSH; 3.58 vs. 2.98 IU/L; p = 0.055). Forty-four men (mean age at exposure, 13.2 years; median serum TCDD, 164 ppt) at 32-39 years of age showed increased total sperm count (272 vs. 191.9 x 10(6); p = 0.042), total motile sperm count (105 vs. 64.9 x10(6); p = 0.036), FSH (4.1 vs. 3.2 UI/L; p = 0.038), and reduced estradiol (74.4 vs. 92.9 pmol/L; p < 0.001). No effects were observed in 20 men, 40-47 years of age, who were exposed to TCDD (median, 123 ppt) as adults (mean age at exposure, 21.5 years). CONCLUSIONS: Exposure to TCDD in infancy reduces sperm concentration and motility, and an opposite effect is seen with exposure during puberty. Exposure in either period leads to permanent reduction of estradiol and increased FSH. These effects are permanent and occur at TCDD concentrations < 68 ppt, which is within one order of magnitude of those in the industrialized world in the 1970s and 1980s and may be responsible at least in part for the reported decrease in sperm quality, especially in younger men.

Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population.

Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for assessing human exposure to PAHs. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) uses OH-PAHs to establish reference range concentrations for the US population, and to set benchmarks for future epidemiologic and biomonitoring studies. For the years 2001 and 2002, 22 OH-PAH metabolites were measured in urine specimens from 2748 NHANES participants. Percentages of samples with detectable levels ranged from nearly 100% for metabolites of naphthalene, fluorene, phenanthrene, and pyrene, to less than 5% for metabolites from parent compounds with higher molecular weight such as chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The geometric mean for 1-hydroxypyrene (1-PYR)--the most commonly used biomarker for PAH exposure--was 49.6 ng/L urine, or 46.4 ng/g creatinine. Children (ages 6-11) generally had higher levels than did adolescents (ages 12-19) or adults (ages 20 and older). Model-adjusted, least-square geometric means for 1-PYR were 87, 53 and 43 ng/L for children, adolescents (ages 12-19) and adults (ages 20 years and older), respectively. Log-transformed concentrations for major detectable OH-PAHs were significantly correlated with each other. The correlation coefficients between 1-PYR and other metabolites ranging from 0.17 to 0.63 support the use of 1-PYR as a useful surrogate representing PAH exposure.

Total TEQ reference range (PCDDs, PCDFs, cPCBs, mono-PCBs) for the US population 2001-2002.

We report reference ranges for the total toxic equivalency (TEQ) and TEQ sub-fractions of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), coplanar biphenyls (cPCBs), and mono-ortho-substituted biphenyls (mPCBs) in a statistically designed sampling of the US population in 2001-2002. The TEQ and TEQ sub-fractions have been stratified by age, sex, and race/ethnicity. The TEQ levels are lower using the 2005 toxic equivalency factors (TEFs) compared to using the 1998 TEF values, principally due to the much lower 2005 TEF values assigned to the mPCBs. Mexican Americans (MA) have significantly lower TEQ levels than both non-Hispanic whites (NHW) and non-Hispanic blacks (NHB). Using the 1998 or 2005 TEF values, males and females have nearly the same distribution of TEQ sub-fractions. We found a significant increase in TEQ levels with age for males, females, and NHW. About 80-90% of the total TEQ can be estimated by using seven congeners, namely 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,6,7,8-HxCDD, 2,3,4,7,8-PeCDF, PCB-126, PCB-118, and PCB-156. We also measured geometric mean TEQ levels in pooled samples from the US population. The geometric mean TEQ levels also increase with age. In the youngest age group (12-19 years), the TEQ levels were higher in males than in females while females had higher TEQ levels than males in all older age groups. In the pools, as age increases the percent contribution of the PCDD TEQ levels increases while the percent contribution of the PCDF TEQ levels decreases for all race/ethnicity and sex strata.

Concentration of polybrominated diphenyl ethers (PBDEs) in household dust from various countries.

Seven polybrominated diphenyl ether (PBDE) congeners were measured in the particulate fraction (<2mm) of household dust samples (n=40), collected in four different countries (Australia, Germany, Great Britain, and United States). Dust samples from Germany contained the lowest concentrations of total PBDEs (median: 74 ng/g, range: 17-550 ng/g dust). Australian dust contained the second lowest concentration (median: 1200 ng/g, range: 500-13,000 ng/g dust). The dust from the United States and Great Britain contained the highest measured amounts of total PBDEs (US median: 4200 ng/g dust, range: 520-29,000 ng/g; Great Britain median: 10,000 ng/g, range: 950-54,000 ng/g). Daily intake of PBDEs has been estimated from published reference values on daily dust intake rates. The highest daily intake of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) found was in the United States (<1-330 ng/day) and the lowest was in Germany (<1-2 ng/day). The PBDE congeners present in commercially available pentabromodiphenyl ether were the highest in concentration in the United States, and the congener distribution was similar to that of the technical preparation (i.e., 2,2',4,4',5-pentabromodiphenyl ether [BDE-99] was similar in concentration to that of BDE-47). We conclude that further studies are required to investigate human indoor exposure to PBDEs across countries and to determine the risk factors related to indoor design factors.

A gas chromatography-isotope dilution high-resolution mass spectrometry method for quantification of isomeric benzo[a]pyrene diol epoxide hemoglobin adducts in humans.

We developed a gas chromatography-isotope dilution high-resolution mass spectrometry (GC-ID-HRMS) method for quantifying isomers of benzo[a]pyrene (BaP) tetrol metabolites resulting from hydrolysis of benzo[a]pyrene-diol-epoxide hemoglobin (BaPDE-Hb) adducts. Acid hydrolysis of BPDE-Hb adducts extracted from human blood samples yielded isomers of benzo[a]pyrene-tetrahydrotetrols, (+/-)-BaP-r-7,t-8,t-9,c-10-tetrol (BPTI-1), (+/-)-BaP-r-7,t-8,t-9,t-10-tetrol (BPTI-2), (+/-)-BaP-r-7,t-8,c-9,t-10-tetrol (BPTII-1), and (+/-)-BaP-r-7,t-8,c-9,c-10-tetrol (BPTII-2). The isomeric BaP tetrols were isolated from the matrix by liquid-liquid extraction, and then further purified by solid-phase extraction. Following silylation with N-methyl-N-(trimethylsilyl)-trifluoroacetamide, the analytes were measured by GC-HRMS, using electron ionization. We have found detectable concentrations in the low fmol range for BPTII-1 and BPTI-1 in all donors tested. The mean BaP adduct levels for smoking donors (n = 9) were 0.022 fmol/mg hemoglobin for BPTII-1 and 0.070 fmol/mg hemoglobin for BPTI-1. The mean BaP adduct levels with hemoglobin for non smoking donors (n = 6) was 0.021 fmol/mg hemoglobin for BPTII-1 and 0.105 fmol/mg hemoglobin for BPTI-1.

Polybrominated diphenyl ether levels in the blood of pregnant women living in an agricultural community in California.

BACKGROUND: Recent studies have raised concerns about polybrominated diphenyl ether (PBDE) flame retardant exposures to pregnant women and women of child-bearing age in the United States. Few studies have measured PBDEs in immigrant populations. OBJECTIVES: Our goal was to characterize levels of seven PBDE congeners, polychlorinated biphenyl (PCB)-153, and polybrominated biphenyl (PBB)-153 in plasma from 24 pregnant women of Mexican descent living in an agricultural community in California. RESULTS: The median concentration of the sum of the PBDE congeners was 21 ng/g lipid and ranged from 5.3 to 320 ng/g lipid. Consistent with other studies, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) was found at the highest concentration (median = 11 ng/g lipid; range, 2.5-205) followed by 2,2',4,4',5-pentabromobiphenyl (BDE-99) (median = 2.9 ng/g lipid; range, 0.5-54), 2,2',4,4',5-pentaBDE (BDE-100) (median = 1.8 ng/g lipid; range, 0.6-44), and 2,2',4,4',5,5'-hexaBDE (BDE-153) (median = 1.5 ng/g lipid; range, 0.4-35). Levels of PCB-153 (median= 4.4 ng/g lipid; range, < 2-75) were lower than U.S. averages and uncorrelated with PBDE levels, suggesting different exposure routes. CONCLUSIONS: The overall levels of PBDEs found were lower than levels observed in other U.S. populations, although still higher than those observed previously in Europe or Japan. The upper range of exposure is similar to what has been reported in other U.S. populations. PBDEs have been associated with adverse developmental effects in animals. Future studies are needed to determine the sources and pathways of PBDE exposures and whether these exposures have adverse effects on human health.

Serum dioxin concentrations and quality of ovarian function in women of Seveso.

BACKGROUND: Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with alterations in ovarian function and hormones in animals, it has not been studied in humans. On 10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later, we initiated the Seveso Women's Health Study to study reproductive health. OBJECTIVE: We related TCDD levels measured in sera collected near the time of explosion and ovarian function (ovarian cysts, ovarian follicles, ovulation rate, serum hormones) at follow-up. METHODS: We included 363 women who were 20-40 years of age and nonusers of oral contraceptives. We examined the relationship of 1976 serum TCDD levels with ultrasound-detected ovarian follicles among 96 women in the menstrual follicular phase and serum hormone levels (estradiol, progesterone) among 129 women in the menstrual luteal phase at follow-up. Ovulation was defined by serum progesterone levels > 3 ng/mL. RESULTS: The median serum TCDD level was 77.3 ppt, lipid-adjusted. Serum TCDD was not associated with number or size of ovarian follicles. Of women in the luteal phase, 87 (67%) ovulated. Serum log(10)TCDD was not associated with odds of ovulation [adjusted odds ratio = 0.99; 95% confidence interval (CI), 0.5 to 1.9]. Among those who had ovulated, serum log(10)TCDD was not associated with serum progesterone [adjusted beta (adj-beta ) = -0.70; 95% CI, -2.4 to 1.0] or estradiol (adj-beta = -1.81; 95% CI, -10.4 to 6.8). CONCLUSIONS: We found no clear evidence that 1976 TCDD exposure was associated with ovarian function 20 years later in women exposed to relatively high levels in Seveso, Italy.

Determinants of prenatal exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in an urban population.

BACKGROUND: Recent studies have reported blood levels of polybrominated diphenyl ethers (PBDEs) in the U.S. population. Information about neonatal levels and about the relationship to polychlorinated biphenyls (PCBs) exposures is limited. OBJECTIVES: The objective was to characterize levels and determinants of fetal exposure to PBDEs and PCBs among newborns from Baltimore, Maryland. METHODS: We analyzed umbilical cord blood for eight PBDEs and 35 PCBs from infants delivered at the Johns Hopkins Hospital. Maternal and infant characteristics were abstracted from medical records. RESULTS: Ninety-four percent of cord serum samples had quantifiable levels of at least one PBDE congener, and > 99% had at least one detectable PCB congener. PBDE concentrations in cord blood were similar to those reported in other studies from North America. Strong correlations were observed within but not across PCB and PBDE classes. Multivariate models showed that many factors independently predicted exposure to BDE-47, BDE-100, and BDE-153 and CB-118, CB-138/158, CB-153, and CB-180. Generally, infants of Asian mothers had lower PBDE and PCB levels, and infants of smokers had higher levels. Increased maternal body mass index was associated with lower levels of PCBs but not PBDEs. Levels of PCBs but not PBDEs were lower in births from married and multiparous mothers. Increased maternal age was associated with higher PCB levels but lower PBDE levels. CONCLUSIONS: Although many of the factors we investigated were independent predictors of both PBDE and PCB levels, in some cases the direction of associations was different. More research is needed to better understand the sources and pathways of PBDE exposure.

Geometric mean estimation from pooled samples.

Biomonitoring for environmental chemicals presents various challenges due to the expense of measuring some compounds and the fact that in some samples the levels of many compounds may be below the limit of detection (LOD) of the measuring instrument. Even though various statistical methods have been developed to address issues associated with data being censored because results were below the LOD, the expense of measuring many compounds in large numbers of subjects remains a challenge. One solution to these challenges is to use pooled samples. There are many problems associated with the use of pooled samples as compared with individual samples, but using pooled samples can sometimes reduce the number of analytical measurements needed. Also, because pooled samples often have larger sample volumes, using pooled samples can result in lower LODs and thereby decrease the likelihood that results will be censored. However, many data sets obtained from environmental measurements have been shown to have a log-normal distribution, so using pooled samples presents a new problem: The measured value for a pooled sample is comparable to an arithmetic average of log-normal results and thus represents a biased estimate of the central tendency of the samples making up the pool. In this paper, we present a method for correcting the bias associated with using data from pooled samples with a log-normal distribution. We use simulation experiments to demonstrate how well the bias-correction method performs. We also present estimates for levels of PCB 153 and p,p'-DDE using data from pooled samples from the 2001 to 2002 National Health and Nutrition Examination Surveys.

Assigning concentration values for dioxin and furan congeners in human serum when measurements are below limits of detection: an observational approach.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in dietary sources for humans have been declining over the previous two decades. These declines have been accompanied by decreases in concentrations of these compounds in humans, as evidenced by measurements in blood and milk. Because of the decreasing concentrations of PCDD/PCDFs in the environment and in humans, measuring PCDD/PCDF congeners in humans has become increasingly difficult, despite advances in analytic methods. An observational approach was recently described to address the quandary of non-detectable results in determining toxic equivalents. This approach, called the congener ratio approach, is specifically for cases where concentrations of 2,3,7,8-TCDD (TCDD) are below the limit of detection (LOD), and where concentrations of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD) are equal to or above the LOD. Development of this approach relied on evaluating data on measured concentrations of TCDD and PeCDD in human serum from the general population. The congener ratio approach for TCDD and PeCDD was based on the concentration of TCDD being approximately 40% that of PeCDD in serum from the general population. Additional analyses presented here reveal that when concentrations of both congeners are above the LOD, the data appear to generally support the congener ratio approach for TCDD and PeCDD, with the caveat that gender may affect the ratio. However, the TCDD/PeCDD relation is less clear when TCDD is less than the LOD; in this situation, the relation overpredicts levels of TCDD approximately 80% of the time for the 2001-2002 NHANES database. Using the congener ratio approach for other PCDD/PCDF congeners requires assessing the correlation and the frequency of detection for both TCDD and PeCDD.

Calculation of serum "total lipid" concentrations for the adjustment of persistent organohalogen toxicant measurements in human samples.

Persistent organohalogen toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin or polychlorinated biphenyls measured in human serum are often expressed on a lipid weight basis, most commonly by dividing the toxicants' concentration by the weight of total lipids in the sample. Therefore, the manner in which this lipid adjustment is calculated may influence the final reported result. Gravimetric total lipid assays have been used, but they are time-consuming and sometimes may be ill-defined. Consequently, alternative methods using enzymatic assays have been developed based on summing the individual lipid species measured. Recent reports, however, have suggested that significantly different total lipid results may be obtained when using alternative formulae in a summation approach. In this report, we summarize the results obtained from lipid measurements of nearly 900 samples made as part of a study of a group of older American men (mean age 62 years), and we compare our total lipid estimates obtained by using both our standard and "short" formula (the latter based on total cholesterol and triglycerides only) with results obtained using the recently proposed alternative formulae. Our findings indicate that both our long and short formulae provide similar estimates of serum total lipid concentrations, and that differences observed in lipid estimates when using the newer alternative summation methods may reflect differences in how the term "total lipid" is defined, especially with regard to the need to include the contribution of the weight of the cholesterol ester fatty acids in the calculation.