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Larry L Needham

Publications and source records attributed to Larry L Needham.

At least 19 recordsLinked to original sources
PubMed2003

New high-resolution mass spectrometric approach for the measurement of polychlorinated biphenyls and organochlorine pesticides in human serum.

To increase our analytical throughput for measuring polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides without sacrificing data quality, we have developed and validated a combined PCB/OC pesticide gas chromatography-high-resolution mass spectrometry (GC-HRMS) analysis. In a single GC-HRMS analysis, both selected PCBs and OC pesticides are detected and quantified. Previously, this has been difficult, if not impossible, because of the major difference in masses of the most abundant electron-impact ions. However, we have identified slightly less abundant ions to monitor that allow us to successfully combine these analytes into a single analysis without sacrificing any analytical sensitivity or instrument reliability. Consequently, we have been able to double our analytical throughput by modification of mass spectrometric parameters alone. Our new methodology has been validated against our current GC-HRMS method, which entails using two separate injections, one for PCB analysis and one for OC pesticide analysis. The two methods differ by less than 4% overall, with no systematic bias. We used this method to analyze approximately 350 serum samples over a period of several months. We found that our new method was as reliable in automated, overnight runs as our current method.

Gas Chromatography-Mass Spectrometry↗
PubMed2003

Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry.

Phthalates are widely used as industrial solvents and plasticizers, with global use exceeding four million tons per year. We improved our previously developed high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometric (HPLC-APCI-MS/MS) method to measure urinary phthalate metabolites by increasing the selectivity and the sensitivity by better resolving them from the solvent front, adding three more phthalate metabolites, monomethyl phthalate (mMP), mono-(2-ethyl-5-oxohexyl)phthalate (mEOHP) and mono-(2-ethyl-5-hydroxyhexyl)phthalate (mEHHP); increasing the sample throughput; and reducing the solvent usage. Furthermore, this improved method enabled us to analyze free un-conjugated mono-2-ethylhexyl phthalate (mEHP) by eliminating interferences derived from coelution of the glucuronide-bound, or conjugated form, of the mEHP on measurements of the free mEHP. This method for measuring phthalate metabolites in urine involves solid-phase extraction followed by reversed-phase HPLC-APCI-MS/MS using isotope dilution with (13)C(4) internal standards. We further evaluated the ruggedness and the reliability of the method by comparing measurements made by multiple analysts at different extraction settings on multiple instruments. We observed mMP, monoethyl phthalate (mEP), mono-n-butyl phthalate (mBP), monobenzyl phthalate (mBzP), mEHP, mEHHP and mEOHP in the majority of urine specimens analyzed with DEHP-metabolites mEHHP and mEOHP present in significantly higher amounts than mEHP.

Atmospheric Pressure↗
PubMed2003

Prenatal exposure to low-level polychlorinated biphenyls in relation to mental and motor development at 8 months.

The relation between exposure to low levels of polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, and cognitive and motor development in young children has been examined in several studies, and results have varied. The authors evaluated the association between prenatal exposure to PCBs and children's neurodevelopment using data from the Collaborative Perinatal Project. Pregnant women were enrolled from 1959 to 1965 from 12 sites across the United States. PCBs were measured in maternal serum taken during pregnancy. To measure children's mental and psychomotor development at 8 months of age, the authors administered the Bayley Scales of Infant Development (means, 87 (standard deviation, 15) and 88 (standard deviation, 18), respectively). Overall, they did not observe a relation between prenatal PCB exposure and children's mental or psychomotor scores (n = 1,207; multivariate adjusted beta = 0.1 point per micro g/liter increase of PCB, p = 0.71, and beta = 0.5, p = 0.14, respectively). The PCB-psychomotor score relation varied by study center (p < 0.05): The association was direct in some centers, inverse in others. This could not be attributed to variation in the timing or measurement of the child's neurodevelopment or analysis of PCBs because these were standardized across centers. The reasons for variation in results within this study and across other studies remain unclear.

Adult↗
PubMed2003

Attenuated growth of breast-fed children exposed to increased concentrations of methylmercury and polychlorinated biphenyls.

Breast-feeding has been linked to slowed postnatal growth. Although the basis for this "weanling's dilemma" is unclear, environmental contaminants in human milk may be of relevance. We studied a Faroese birth cohort of 182 singleton children, born at term in 1994-95. Concentrations of mercury in cord blood and of polychlorinated biphenyls in maternal milk were measured, and duration of breast-feeding was recorded. At 18 months, children who had been exclusively breast-fed for at least 6 months weighed 0.59 kg less [95% confidence interval (CI) = 0.03, 1.16 kg] and were 1.50 cm [95% CI = 0.52, 2.47 cm] shorter than those not breast-fed. However, calculated transfer of contaminants from human milk fully explained the attenuated growth. Irrespective of duration of breast-feeding, a doubling of the mercury concentration in cord blood was associated with a decrease in weight at 18 months by 0.19 kg (95% CI = 0.03, 0.35 kg) and in height by 0.26 cm (95% CI = -0.02, 0.55 cm). Weight and height at 42 months showed the same tendencies, but the main effect occurred before 18 months of age. Thus, in communities with increased contaminant exposures, risks associated with lactational transfer of toxicants to the infant must be considered when judging the benefits of prolonged breast-feeding.

Body Height↗
PubMed2003

Comprehensive solid-phase extraction method for persistent organic pollutants. Validation and application to the analysis of persistent chlorinated pesticides.

The Centers for Disease Control and Prevention (CDC) is involved in many epidemiological studies regarding the measurement of chlorinated pesticides and polychlorinated biphenyls in specimens obtained from humans. In addition to these commonly determined analytes, there is a need to include additional persistent organic pollutants (POPs) in our analyses, which further stresses the analyses because sample volumes remain small. Thus, a single method of analysis for all POPs in human serum is needed. CDC has recently developed a semiautomated and comprehensive solid-phase extraction method for POPs. The method is comprehensive since it was optimized for the extraction of many different POP compound classes. We then developed a purification and fractionation scheme that allows (a) separation of different compound classes by particular functionalities and (b) purification of those fractions to remove coextracted interferences. This paper describes the first step in the semiautomated comprehensive extraction and multiple fractionation method developed by CDC for monitoring POPs. In this paper, we validate the analysis of the persistent chlorinated pesticides, a compound class difficult to examine because of their structural diversity, in human plasma. The method was validated against an existing CDC method by using a spiked quality-control serum pool. The concentrations determined for all analytes using both methods were within 2%-14% relative standard deviations. A multilevel (i.e., 3-4 point) matrix spike showed good linearity for the analytes tested (r2 = 0.978-0.999). The method was then applied to 40-year-old archived plasma samples for the quantitative analysis of selected chlorinated pesticides. Mean recoveries of the 13C-labeled internal quantification standards ranged from 64% to 123% for the 11 monitored pesticides. The overall method proved to be robust by handling old coagulated plasma samples. It allowed faster throughput of samples than our previous methods and provided cleaner samples with less frequent interferences or background as analyzed by high-resolution mass spectrometry. The method represents a preliminary step in establishing an automated, comprehensive multiresidue analysis method for POPs in human serum.

Automation↗
PubMed2003

Nondietary ingestion of pesticides by children in an agricultural community on the US/Mexico border: preliminary results.

An environmental measurement and correlation study of nondietary ingestion of pesticides was carried out in a colonia in south Texas. The purpose of the study was to evaluate young children's exposure to environmental levels of organophosphate (OP) pesticides in the household. Samples were collected to measure levels of OP pesticides in housedust and on children's hands. These, in turn, were compared to levels of OP pesticide metabolites in urine. A total of 52 children, 25 boys and 27 girls, participated in the spring and summer of 2000. The children were 7-53 months of age at the time of recruitment. Univariate and multivariate regression analyses were carried out using SAS statistical software. Seventy-six percent of housedust samples and 50% of hand rinse samples contained OP pesticides. All urine samples had at least one metabolite and over 95% had at least two metabolites above the limit of detection (LOD). Total OP loadings in the housedust ranged from nondetectable (nd) to 78.03 nmol/100 cm(2) (mean=0.15 nmol/100 cm(2); median=0.07 nmol/100 cm(2)); total OP loadings on the children's hands ranged from nd to 13.40 nmol/100 cm(2) (mean=1.21 nmol/100 cm(2); median=1.41 nmol/100 cm(2)), and creatinine corrected urinary levels (nmol/mol creatinine) of total OP metabolites ranged from 3.2 to 257 nmol/mol creatinine (mean=42.6; median 27.4 nmol/mol creatinine). Urinary metabolites were inversely associated with the age of the child (in months) with the parameter estimate (pe)=-2.11, P=0.0070, and 95% confidence interval -3.60 to -0.61. The multivariate analysis observed a weak association between concentrations of OP pesticides in housedust, loadings in housedust, and concentration on hands, hand surface area, and urinary levels of OP metabolites. However, hand loadings of OP pesticides were more strongly associated (r(2)=0.28; P=0.0156) with urinary levels of OP metabolites (pe=6.39; 95% CI 0.98-11.80). This study's preliminary findings suggest that surface loadings of pesticides, on hands, are more highly correlated with urinary bioassays and, therefore, may be more useful for estimation of exposure in epidemiologic studies than levels of pesticides in housedust.

Administration, Cutaneous↗
PubMed2003

Urinary and serum concentrations of seven phytoestrogens in a human reference population subset.

Diets rich in naturally occurring plant estrogens (phytoestrogens) are strongly associated with a decreased risk for cancer and heart disease in humans. Phytoestrogens have estrogenic and, in some cases, antiestrogenic and antiandrogenic properties, and may contribute to the protective effect of some diets. However, little information is available about the levels of these phytoestrogens in the general US population. Therefore, levels of phytoestrogens were determined in urine (N=199) and serum (N=208) samples taken from a nonrepresentative subset of adults who participated in NHANES III, 1988-1994. The phytoestrogens quantified were the lignans (enterolactone, enterodiol, matairesinol); the isoflavones (genistein, daidzein, equol, O-desmethylangolensin); and coumestrol (urine only). Phytoestrogens with the highest mean urinary levels were enterolactone (512 ng/ml), daidzein (317 ng/ml), and genistein (129 ng/ml). In serum, the concentrations were much less and the relative order was reversed, with genistein having the highest mean level (4.7 ng/ml), followed by daidzein (3.9 ng/ml) and enterolactone (3.6 ng/ml). Highly significant correlations of phytoestrogen levels in urine and serum samples from the same persons were observed for enterolactone, enterodiol, genistein, and daidzein. Determination of phytoestrogen concentrations in large study populations will give a better insight into the actual dietary exposure to these biologically active compounds in the US population.

Adult↗
PubMed2003

Risk of non-Hodgkin's lymphoma and prediagnostic serum organochlorines: beta-hexachlorocyclohexane, chlordane/heptachlor-related compounds, dieldrin, and hexachlorobenzene.

Increases in non-Hodgkin's lymphoma (NHL) incidence and mortality rates during the past few decades remain largely unexplained. Studies suggest that organochlorine pesticides may contribute to an increased risk of NHL. In 1974, serum samples were obtained from 25,802 participants in the Campaign Against Cancer and Stroke in Washington County, Maryland (USA), and cryopreserved for future study. We measured prediagnostic levels of chlordane, lindane (gamma-hexachlorocyclohexane), beta-hexachlorocyclohexane, transnonachlor, heptachlor, heptachlor epoxide, oxychlordane, dieldrin, and hexachlorobenzene in serum samples of 74 cases of NHL and 147 matched controls. Previously, we found an association between NHL and serum levels of total PCBs (polychlorinated biphenyls), but not DDT (dichlorodiphenyltrichloroethane) and related compounds. In this instance, there was no evidence of an association between NHL risk and serum levels of any of the individual lipid- and recovery-corrected organochlorines that we evaluated, nor of the summed chlordane-related compounds (transnonachlor, heptachlor, heptachlor epoxide, oxychlordane). These findings do not support the hypothesis that the organochlorine compounds included in this study are strongly linked to the development of NHL. The possibility of a weak association cannot be excluded by these data.

Case-Control Studies↗
PubMed2003

Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers.

Phthalates are a group of industrial chemicals with many commercial uses, such as solvents, additives, and plasticizers. For example, di-(2-ethylhexyl) phthalate (DEHP) is added in varying amounts to certain plastics, such as polyvinyl chloride, to increase their flexibility. In humans, phthalates are metabolized to their respective monoesters, conjugated, and eliminated. However, despite the high production and use of DEHP, we have recently found that the urinary levels of the DEHP metabolite mono-(2-ethylhexyl) phthalate (MEHP) in 2,541 persons in the United States were lower than we anticipated, especially when compared with urinary metabolite levels of other commonly used phthalates. This finding raised questions about the sensitivity of this biomarker for assessing DEHP exposure. We explored the utility of two other DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), as additional DEHP biomarkers. These metabolites are formed by oxidative metabolism of MEHP. In urine from 62 people, both the range and the mean urinary levels of MEOHP and MEHHP were on average 4-fold higher than those of MEHP; the mean of the individual ratios of MEHHP/MEOHP, MEHHP/MEHP, and MEOHP/MEHP were 1.4, 8.2, and 5.9, respectively. These data suggest that MEOHP and MEHHP are more sensitive biomarkers of exposure to DEHP than is MEHP. These findings also suggest a predominant human metabolic route for DEHP hydrolysis to MEHP followed by oxidation of MEHP; they also imply that a similar mechanism may be relevant for other high-molecular-weight phthalates, such as di-n-octyl, di-isononyl, and di-isodecyl phthalates.

Biomarkers↗
PubMed2003

Maternal serum dioxin levels and birth outcomes in women of Seveso, Italy.

2,3,7,8-Tetrachlorodibenzo-(italic)para(/italic)-dioxin (TCDD), a ubiquitous environmental contaminant, is associated with increased fetal loss and reduced birth weight in animal studies. In 1976, an explosion at a trichlorophenol plant near Seveso, Italy, resulted in the highest TCDD exposure known in human residential populations. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of women who resided in the most contaminated areas, zones A and B. We examined the relation of pregnancy outcome in 510 women (888 total pregnancies) to maternal TCDD levels measured in serum collected shortly after the explosion. Ninety-seven pregnancies (10.9%) ended as spontaneous abortions (SABs). There was no association of log(subscript)10(/subscript) TCDD with SAB [adjusted odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.6-1.2], with birth weight (adjusted beta = -4 g; 95% CI, -68 to 60), or with births that were small for gestational age (SGA) (adjusted OR = 1.2; 95% CI, 0.8-1.8). However, associations with birth weight (adjusted beta = -92 g; 95% CI, -204 to 19) and with SGA (adjusted OR = 1.4; 95% CI, 0.6-2.9) were stronger for pregnancies within the first 8 years after exposure. TCDD was associated with a 1.0-1.3 day nonsignificant adjusted decrease in gestational age and a 20-50% nonsignificant increase in the odds of preterm delivery. It remains possible that the effects of TCDD on birth outcomes are yet to be observed, because the most heavily exposed women in Seveso were the youngest and the least likely to have yet had a pregnancy.

Abortion, Spontaneous↗
PubMed2002

Guidelines for analysis of human milk for environmental chemicals.

When analyzing human milk for environmental chemicals, in either a monitoring or research project, researchers must ensure that the technique used for measuring the target analytes complies with certain analytical criteria and that a quality control/quality assurance program is in place. In this report, these analytical criteria and the accompanying quality assurance program are elaborated in more detail. Examples of representative methods are also given for the determination of a number of classes of chemicals of environmental concern, such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, polychlorinated biphenyls, volatile organics, and halogenated flame retardants. Most of these techniques are physical/chemical in nature, but the possibility of the use of bioassays for screening of analytes in human milk is noted. The described methods are not exclusive, but any laboratory undertaking the analysis of human milk should demonstrate proficiency in their execution. This is usually accomplished by producing reliable data in interlaboratory studies. Human milk is an ideal matrix for estimating exposure to certain environmental chemicals, and researchers must ensure that the techniques used to determine these compounds adhere to known and accepted analytical requirements.

Environmental Monitoring↗
PubMed2002

A multi-analyte method for the quantification of contemporary pesticides in human serum and plasma using high-resolution mass spectrometry.

We have developed a sensitive and accurate analytical method for quantifying 29 contemporary pesticides in human serum or plasma. These pesticides include organophosphates, carbamates, chloroacetanilides, and synthetic pyrethroids among others and include pesticides used in agricultural and residential settings. Our method employs a simple solid-phase extraction followed by a highly selective analysis using isotope dilution gas chromatography-high-resolution mass spectrometry. Our method is very accurate, has limits of detection in the low pg/g range and coefficients of variation of typically less than 20% at the low pg/g end of the method linear range. We have used this method to measure plasma pesticide concentrations in females living in an urban area. We found detectable concentrations of carbaryl/naphthalene, propoxur, bendiocarb, chlorpyrifos, diazinon, dicloran, captan and folpet or their metabolites in more than 20% of the plasma samples tested.

Calibration↗
PubMed2002

Analytical methods for biological monitoring of exposure to pesticides: a review.

Synthetic pesticides have been used since in the early to mid twentieth century. In the US alone, over 800 pesticide active ingredients are formulated in about 21,000 different commercial products. Although many public health benefits have been realized by the use of pesticides, their potential impact on the environment and public health is substantial. For risk assessment studies, exposure assessment is an integral component, which has unfortunately, often been weak or missing. In the past several decades, researchers have proposed to fill these missing data gaps using biological monitoring of specific markers related to exposures. In this paper, we present a review of existing analytical methodology for the biological monitoring of exposure to pesticides. We also present a critical assessment of the existing methodology and explore areas in which more research is needed.

Environmental Monitoring↗
PubMed2002

Serum dioxin concentrations and menstrual cycle characteristics.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread industrial environmental contaminant. Animal studies suggest that TCDD exposure alters the estrus cycle. Twenty years after a 1976 industrial explosion in Seveso, Italy, the authors interviewed female residents to determine whether there was an association between TCDD exposure and current menstrual cycle characteristics. The authors analyzed serum samples collected soon after the explosion to quantify individual TCDD levels. Among women who were premenarcheal at the time of the explosion, a 10-fold increase in serum TCDD level was associated with a lengthening of the menstrual cycle by 0.93 days (95% confidence interval (CI): -0.01, 1.86) and a reduction in the odds of scanty menstrual flow (adjusted odds ratio = 0.33, 95% CI: 0.10, 1.06). However, among women who were postmenarcheal at the time of the explosion, TCDD was not associated with menstrual cycle length (adjusted beta = -0.03 days, 95% CI: -0.61, 0.54) or scantiness of flow (adjusted odds ratio = 1.36, 95% CI: 0.70, 2.64). In both menarche groups, TCDD levels were associated with decreased odds of having irregular cycles (adjusted odds ratio = 0.46, 95% CI: 0.23, 0.95) but were not related to days of flow (adjusted beta = 0.16 days, 95% CI: -0.08, 0.41). These results are consistent with effects of TCDD on ovarian function noted in some animal species and with greater sensitivity to TCDD during development.

Adult↗
PubMed2002

Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring.

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is a metabolite of the insecticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and is a ubiquitous environmental contaminant. Nearly everyone in the United States has a detectable serum level of DDE. DDE was recently found to inhibit binding of androgen to its receptor and to block androgen action in rodents. Normal development of male genitalia in mammals depends on androgen action. The authors used stored serum samples to examine the relation between maternal DDE levels during pregnancy and adjusted odds of cryptorchidism (n = 219), hypospadias (n = 199), and polythelia (extra nipples) (n = 167) among male offspring, using a nested case-control design with one control group (n = 552). Subjects were selected from the Collaborative Perinatal Project, a US birth cohort study begun in 1959-1966, when DDE levels were much higher than they are at present. Compared with boys whose mother's recovery-adjusted serum DDE level was less than 21.4 microg/liter, boys with maternal levels greater than or equal to 85.6 microg/liter had adjusted odds ratios of 1.3 (95% confidence interval (CI): 0.7, 2.4) for crypt-orchidism, 1.2 (95% CI: 0.6, 2.4) for hypospadias, and 1.9 (95% CI: 0.9, 4.0) for polythelia. For cryptorchidism and polythelia, the results were consistent with a modest-to-moderate association, but in no instance was the estimate very precise. The results were inconclusive.

Adult↗
PubMed2002

Investigation of the relation between self-reported food consumption and household chemical exposures with urinary levels of selected nonpersistent pesticides.

Concerns about pesticide exposure through food consumption have increased during the past several years. The main objective of our study was to determine whether we could use data from the Third National Health and Nutrition Examination Survey (NHANES III) to detect a relation between self-reported food consumption--particularly consumption of fruits, vegetables, and bread products--and urinary levels of pesticides or their metabolites in a population of 978 adults living in the US. A secondary objective was to investigate whether these urine levels differed for people who reported exposure to selected common household chemicals including bug or insect spray, weed killer, and mothballs or crystals. We used monthly food frequency data from the NHANES III, 1988-1994. Urinary pesticide/metabolite levels and information about chemical exposures were taken from the Priority Toxicant Reference Range Study (a component of the NHANES III). Six pesticides or their metabolites were detected in at least 50% of the sample, three of which--1-naphthol (86.4%), pentachlorophenol (62.5%), and 3,5,6-trichloro-2-pyridinol (82.0%)--were possibly related to food consumption. We were unable to detect a relation between self-reported food consumption and their urinary levels. This may be due more to the limitations of the datasets than to a lack of a relation between food consumption and urine pesticide/metabolite levels. We did find that people who reported recently using selected common chemicals had higher geometric mean urine pesticide/metabolite levels than did people who reported not recently using these chemicals.

Adult↗
PubMed2002

Characterization of dioxin exposure in residents of Chapaevsk, Russia.

Since 1967, a chemical plant in the town of Chapaevsk (Samara province, Russia) has produced large amounts of chlorinated compounds and is suspected to be a major source of local environmental dioxin contamination. Dioxins have been detected in the local air, soil, drinking water, vegetables, and cow's milk. Human exposure to dioxins is suspected as a factor in the deteriorating local public health. In an effort to characterize nonoccupational dioxin exposure among local residents, during the summer of 1998, 24 volunteers were recruited to donate blood and to provide information about their residence, employment, demographics, medical history, and dietary habits. Selected polychlorinated dibenzodioxins, dibenzofurans, and coplanar biphenyls were measured in blood serum samples. The mean concentration of total dioxin World Health Organization toxic equivalents (WHO-TEQ(98)) based on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) was 61.2 (range 16.4-168.1) pg/g lipid. Subjects living in close proximity to the plant (less than 5 km) had significantly higher dioxin levels (mean WHO-TEQ(98), 75.7 pg/g lipid), as compared to subjects living more than 5 km from the plant (mean WHO-TEQ(98), 44.1 pg/g lipid) (P<0.04). Comparisons of the study results with available published data indicate that average blood dioxin levels were substantially higher in Chapaevsk residents than in nonoccupationally exposed populations of other parts of Russia, Europe, and North America. Chronic exposures of such magnitude may have appreciable adverse effects on public health.

Adult↗