Biomedical subjects

Larry L Needham

Publications and source records attributed to Larry L Needham.

102 records · Page 6Linked to original sources

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↗

PubMed2002

Analytic considerations for measuring environmental chemicals in breast milk.

The presence of environmental chemicals in human breast milk is of general concern because of the potential health consequence of these chemicals to the breast-fed infant and the mother. In addition to the mother's exposure, several features determine the presence of environmental chemicals in breast milk and their ability to be determined analytically. These include maternal factors and properties of the environmental chemical--both physical and chemical--such as its lipid solubility, degree of ionization, and molecular weight. Environmental chemicals with high lipid solubility are likely to be found in breast milk; they include polyhalogenated compounds such as polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, organochlorine insecticides, and polybrominated diphenylethers. These fat-soluble chemicals are incorporated into the milk as it is synthesized, and they must be measured in accordance with the fat content of the milk to allow for meaningful comparisons within an individual and among populations. Although the analytic approach selected to measure the environmental chemical is predominantly determined by the characteristics of the chemical, the concentration of the chemical in the milk sample and the existence of structurally similar chemicals (e.g., congeners) must be considered as well. In general, the analytic approach for measuring environmental chemicals in breast milk is similar to the approach for measuring the same chemicals in other matrices, except special considerations must be given for the relatively high fat content of milk. The continued efforts of environmental scientists to measure environmental chemicals in breast milk is important for defining the true contribution of these chemicals to public health, especially to the health of the newborn. Work is needed for identifying and quantifying additional environmental chemicals in breast milk from the general population and for developing analytic methods that have increased sensitivity and the ability to speciate various chemicals.

Adult↗

PubMed2002

The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population.

Population-based estimates of environmental exposures using biomarkers can be difficult to obtain for a variety of reasons, including problems with limits of detection, undersampling of key strata, time between exposure and sampling, variation across individuals, variation within individuals, and the ability to find and interpret a given biomarker. In this article, we apply statistical likelihoods, weighted sampling, and regression methods for censored data to the analysis of biomarker data. Urinary metabolites for seven phthalates, reported by Blount et al., are analyzed using these methods. In the case of the phthalates data, we assumed the underlying model to be a log-normal distribution with the mean of the distribution defined as a function of a number of demographic variables that might affect phthalate levels in individuals. Included as demographic variables were age, sex, ethnicity, residency, family income, and education level. We conducted two analyses: an unweighted analysis where phthalate distributions were estimated with changes in the means of these distributions as a function of demographic variables, and a weighted prediction for the general population in which weights were assigned for a subset of the population depending on the frequency of their demographic variables in the general U.S. population. We used statistical tests to determine whether any of the demographic variables affected mean phthalate levels. Individuals with only a high school education had higher levels of di-n-butyl phthalate than individuals with education beyond high school. Subjects who had family income less than $1,500 in the month before sampling and/or only high school education had higher levels of n-butyl benzyl phthalate levels than other groupings. Di(2-ethylhexyl) phthalate was higher in males and/or in urban populations and/or in people who had family income less than $1,500 per month. Our findings suggest that there may be significant demographic variations in exposure and/or metabolism of phthalates and that health-risk assessments for phthalate exposure in humans should consider different potential risk groups.

Adult↗

PubMed2002

Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis.

Adult↗

PubMed2002

Public health decisions: the laboratory's role in the Lorain County, Ohio, investigation.

In 1994 officials from the Ohio Department of Health reported that some residents of Lorain County, Ohio, possibly had been exposed to methyl parathion (MP), a highly toxic restricted-use pesticide. The U.S. Centers for Disease Control and Prevention (CDC) assisted in the investigation by providing epidemiologic and laboratory support to the state and local health departments. Although the initial investigation found MP inside the homes, it was unclear if the residents were exposed. CDC used a new biological monitoring method to measure urinary p-nitrophenol (PNP), the metabolite of MP. This biological monitoring measures the internal dose from exposure to toxic chemicals from all routes. Laboratory analyses demonstrated that the urine of residents contained moderate to high levels of PNP, with median, mean, and highest reported concentrations of 28, 240, and 4,800 g/L, respectively, thus confirming exposure of the residents. Almost 80% of the residents had urinary PNP concentrations above the 95th percentile of the reference range concentrations. This information, combined with other analytical results of air and wipe tests, guided public health officials' decisions about the potential risk in each household. In this article we illustrate the laboratory's role in providing information to assist in making these public health decisions. Furthermore, it illustrates how a multidisciplinary team from various governmental agencies worked together to protect the public's health.

Biomarkers↗

PubMed2002

Measurement of p-nitrophenol in the urine of residents whose homes were contaminated with methyl parathion.

During the last several years, illegal commercial application of methyl parathion (MP) in domestic settings in several U.S. Southeastern and Midwestern States has affected largely inner-city residents. As part of a multiagency response involving the U.S. Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR), and state and local health departments, our laboratory developed a rapid, high-throughput, selective method for quantifying p-nitrophenol (PNP), a biomarker of MP exposure, using isotope dilution high-performance liquid chromatography-tandem mass spectrometry. We measured PNP in approximately 16,000 samples collected from residents of seven different states. Using this method, we were able to receive sample batches from each state; prepare, analyze, and quantify the samples for PNP; verify the results; and report the data to the health departments and ATSDR in about 48 hr. These data indicate that many residents had urinary PNP concentrations well in excess of those of the general U.S. population. In fact, their urinary PNP concentrations were more consistent with those seen in occupational settings or in poisoning cases. Although these data, when coupled with other MP metabolite data, suggest that many residents with the highest concentrations of urinary PNP had significant exposure to MP, they do not unequivocally rule out exposure to PNP resulting from environmental degradation of MP. Even with their limitations, these data were used with the assumption that all PNP was derived from MP exposure, which enabled the U.S. EPA and ATSDR to develop a comprehensive, biologically driven response that was protective of human health, especially susceptible populations, and included clinical evaluations, outreach activities, community education, integrated pest management, and decontamination of homes.

Biomarkers↗

PubMedDate not supplied

Pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Seveso adults and veterans of operation Ranch Hand.

A combined analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in Seveso adults and Ranch Hand veterans found a period of fast elimination within the first 0.27 years after exposure in Seveso, followed by a period of slower elimination between 3 and 16.35 years from exposure. The mean TCDD elimination rate within the first 0.27 years after exposure among six adult males in the Seveso cohort was 2.0646 year(-1) (half-life=0.34 years). The mean rate from 3 to 16.35 years was 0.1011 year(-1) (half-life=6.9 years). The mean Ranch Hand elimination rate, 00924 year(-1) (half-life=6.9 years), measured between 9 and 33 years after exposure, was significantly less than the Seveso mean in the first 0.27 years after exposure, but not significantly different from the Seveso mean between 3 and 16.35 years after exposure. The fast elimination within the first 0.27 years followed by a slower rate after 3 years is consistent with the expected pattern in a two-compartment open model, with a distribution phase of rapid elimination followed by a slower elimination phase.

Accidents, Occupational↗

PubMedDate not supplied

Quantitation of organophosphorus nerve agent metabolites in human urine using isotope dilution gas chromatography-tandem mass spectrometry.

An isotope dilution gas chromatography-tandem mass spectrometric (GC-MS-MS) method was developed for quantitating the urinary metabolites of the organophosphorus nerve agents sarin, soman, tabun (GA), VX, and GF. Urine samples were concentrated by codistillation with acetonitrile, derivatized by methylation with diazomethane, and analyzed by GC-MS-MS. The limits of detection were less than 4 microg/L for all the analytes except for the GA metabolite, which had a limit of detection of less than 20 microg/L.

Calibration↗

PubMedDate not supplied

Quantitation of dialkyl phosphate metabolites of organophosphate pesticides in human urine using GC-MS-MS with isotopic internal standards.

Human exposure to organophosphate pesticides can be estimated from the presence of urinary metabolites. An isotope-dilution gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed for quantitating the six dialkyl phosphate urinary metabolites of at least 29 organophosphate pesticides. Urine samples were spiked with stable isotope analogues of the dialkyl phosphates, evaporated using azeotropic distillation, followed by chemical derivatization of the metabolites to their respective chloropropyl phosphate esters. The chloropropyl phosphate esters were concentrated and then analyzed using GC-MS-MS. The limits of detection (LODs) of the method were in the low-to-mid picogram-per-milliliter range (parts per trillion) with coefficients of variation of less than 20%. The use of stable isotope analogues as internal standards for each of these metabolites allows for the highest degree of accuracy and precision. Additionally, the low LODs allow the use of this method in general population studies.

Environmental Exposure↗

PubMedDate not supplied

Quantitative detection of nine phthalate metabolites in human serum using reversed-phase high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

We developed a highly sensitive method for the quantitative detection of nine phthalate ester metabolites in human serum. This method requires denaturation of the serum enzymes immediately after blood collection to avoid the hydrolysis of the contaminant diester parent compounds introduced during blood collection and storage. Before analysis, the samples were subjected to an enzymatic deconjugation to hydrolyze the glucuronidated phthalate monoesters and a solid-phase extraction to isolate the monoesters from other serum components. The extracts were analyzed using reversed-phase high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The limits of detection of all nine phthalate monoesters in serum were in the low nanogram-per-milliliter range (0.6-1.3 ng/mL). Stable isotope-labeled internal standards for all analytes were used to improve precision and for recovery corrections. This highly selective method permits the analysis of phthalate monoesters without interferences resulting from the hydrolysis of the ubiquitous contaminant phthalate diesters by serum enzymes. In addition, it allows the direct measurement of the active phthalate monoester metabolites reportedly responsible for the reproductive and developmental toxicity of certain phthalates.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Automated solid-phase extraction and quantitative analysis of 14 phthalate metabolites in human serum using isotope dilution-high-performance liquid chromatography-tandem mass spectrometry.

Phthalates are industrial chemicals with many commercial applications. Because of their common usage, the general population is exposed to phthalates. A sensitive and selective analytical method is necessary to accurately determine the phthalate levels in serum. We improved our previously developed analytical method to measure nine phthalate metabolites in human serum by automating the solid-phase extraction (SPE) procedure and by including five additional phthalate metabolites: phthalic acid; mono-isobutyl phthalate, a metabolite of di-isobutyl phthalate; mono-(3-carboxypropyl) phthalate, a major oxidative metabolite of di-n-octyl phthalate; and mono-(2-ethyl-5-oxohexyl) phthalate and mono-(2-ethyl-5-hydroxyhexyl) phthalate, two oxidative metabolites of di-(2-ethylhexyl) phthalate. Automation of the SPE eliminated the human variation associated with the manual SPE, thus improving the reproducibility of the measurements. Additional wash steps during SPE produced cleaner extracts and resulted in higher recoveries (80-99%) than the manual SPE method. Furthermore, the automated SPE method allowed for the unattended extraction of samples, with a concomitant increase in sample throughput compared to the manual SPE method. The method is accurate, precise, and sensitive, with limits of detection in the low nanogram-per-milliliter range.

Carbon Isotopes↗