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L L Needham

Publications and source records attributed to L L Needham.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Assessing children's exposure to hazardous environmental chemicals: an overview of selected research challenges and complexities.

There is renewed interest in the United States regarding characterization of children's exposures to hazardous environmental chemicals. Many studies are currently underway that use novel and innovative approaches to assess childhood exposures to a variety of toxic chemicals, including both persistent and nonpersistent compounds. This article reviews some of the critical challenges that can impede scientifically rigorous studies designed to measure children's environmental exposures. The discussion briefly examines three topical areas: administrative issues (IRB approval, participant incentives, community involvement, and communication of results to research participants and stakeholders); data-collection issues (identifying and recruiting children/families, measuring actual exposures/doses); and issues related to chemical analysis of biological samples (examples of chemicals and chemical classes that can be measured in human tissue and excreta, effects of a child's age on the type and amount of biological samples available for analysis). These research complexities are discussed in the context of developing more effective and efficient exposure assessment methods.

Child↗
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Measurement of bisphenol A levels in human urine.

We report a new approach for assessing human exposure to bisphenol A (BPA) by measuring BPA in urine after enzymatic deglucuronidation. This method involves addition of (13)C(12)-labeled BPA, enzymatic deconjugation, solid-phase extraction, and derivatization with pentafluorobenzyl bromide. The product of the derivatization is separated by gas chromatography followed by mass spectrometric detection using negative chemical ionization and selected ion monitoring. Using this analysis method, urine samples fortified with both a constant level of labeled BPA and a range of unlabeled BPA levels (0.27-10.6 ng/ml) demonstrated constant percentage recovery. In addition, a range of urine sample volumes (0.25-10.0 ml) with constant amounts of added internal standard produced a linear response (r(2)=0.99). The method limit of detection was 0.12 ng/ml. This method was validated by duplicate analyses using gas chromatography coupled to a high-resolution mass spectrometer.

Benzhydryl Compounds↗
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Tetrachloroazobenzene in 3,4-dichloroaniline and its herbicidal derivatives: propanil, diuron, linuron, and neburon.

The presence of 3,3', 4,4'-tetrachloroazobenzene (TCAB) was determined by high performance liquid chromatography in 3, 4-dichloroaniline and herbicides made therefrom. The concentrations of TCAB in 3, 4-dichloroanilines and in different herbicides from a variety of manufacturers ranged from 9 to 1400 micrograms/g (ppm). The chloracnegenic potential of these products, as determined by rabbit ear test, suggests that it is in the same range of 2, 3, 7, 8-tetrachlorodibenzodioxin, a known potent chloracnegenic agent.

Acne Vulgaris↗
PubMedDate not supplied

Half-life of polychlorinated biphenyls in occupationally exposed workers.

In 1977 and 1985, serum polychlorinated biphenyl (PCB) concentrations were determined for 58 workers in a Bloomington, Indiana, factory that used polychlorinated biphenyls (PCBs) in capacitor manufacture until 1977. Less chlorinated PCBs were quantitated as Aroclor 1242, and more highly chlorinated PCBs were quantitated as Aroclor 1254. The median half-life was 2.6 y for Aroclor 1242 and 4.8 y for Aroclor 1254. However, the half-life varied inversely with the initial serum concentration. This pattern may be a result of continued low-level exposure, variation in the time of exposure, or enzyme induction by PCBs.

Adult↗
PubMedDate not supplied

p-Dichlorobenzene exposure among 1,000 adults in the United States.

p-Dichlorobenzene is used widely in the United States as a room deodorizer, a moth repellent, and a precursor for a polymer. In a previous study of selected children in Arkansas, we found that 96% of the children had detectable urinary concentrations of 2,5-dichlorophenol, the metabolite of p-dichlorobenzene. In the current study, we found that, in a sample of 1,000 adults who lived throughout the United States, 98% had detectable levels of 2,5-dichlorophenol in their urine, and 96% had detectable levels of p-dichlorobenzene in their blood. Urinary 2,5-dichlorophenol concentrations ranged up to 8,700 micrograms/l (median and mean concentrations of 30 micrograms/l and 200 micrograms/l, respectively). p-Dichlorobenzene blood concentrations ranged up to 49 micrograms/l, with median and mean concentrations of 0.33 micrograms/l and 2.1 micrograms/l, respectively. The Pearson correlation coefficient for 2,5-dichlorophenol in urine and p-dichlorobenzene in blood was .82 (p < .0001), thus demonstrating a strong association between these exposure measurements. Neither age nor gender was related to urinary 2,5-dichlorophenol or blood p-dichlorobenzene concentrations (p > .40). When these results are viewed with data from other studies, the collective data show that p-dichlorobenzene is a common, worldwide contaminant. The high prevalence of exposure to p-dichlorobenzene, coupled with its potential for adverse health effects, indicate the need for more detailed studies, including studies of long-term health effects on exposed populations.

Adult↗
PubMedDate not supplied

Measurement of eight urinary metabolites of di(2-ethylhexyl) phthalate as biomarkers for human exposure assessment.

Human metabolism of di(2-ethylhexyl) phthalate (DEHP) is complex and yields mono(2-ethylhexyl) phthalate (MEHP) and numerous oxidative metabolites. The oxidative metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono(2-carboxymethylhexyl) phthalate (MCMHP), have been considered to be better biomarkers for DEHP exposure assessment than MEHP because urinary levels of these metabolites are generally higher than MEHP, and their measurements are not subject to contamination. The urinary levels of the above metabolites, and of three other recently identified DEHP oxidative metabolites, mono(2-ethyl-3-carboxypropyl) phthalate (MECPrP), mono-2-(1-oxoethylhexyl) phthalate (MOEHP), and mono(2-ethyl-4-carboxybutyl) phthalate (MECBP), were measured in 129 adults. MECPP, MCMHP and MEHHP were present in all the samples analysed. MEHP and the other oxidative metabolites were detected less frequently: MEOHP (99%), MECBP (88%), MECPrP (84%), MEHP (83%) and MOEHP (77%). The levels of all DEHP metabolites were highly correlated (p<0.0001) with each other, confirming a common parent. The ? and ?-1 oxidative metabolites (MECPP, MCMHP, MEHHP and MEOHP) comprised 87.1% of all metabolites measured, and thus are most likely the best biomarkers for DEHP exposure assessment. The percentage of the unglucuronidated free form excreted in urine was higher for the ester linkage carboxylated DEHP metabolites compared with alcoholic and ketonic DEHP metabolites. The percentage of the unglucuronidated free form excreted in urine was higher for the DEHP metabolites with a carboxylated ester side-chain compared with alcoholic and ketonic metabolites. Further, differences were found between the DEHP metabolite profile between this adult population and that of six neonates exposed to high doses of DEHP through extensive medical treatment. In the neonates, MEHP represented 0.6% and MECPP 65.5% of the eight DEHP metabolites measured compared to 6.6% (MEHP) and 31.8% (MECPP) in the adults. Whether the observed differences reflect differences in route/duration of the exposure, age and/or health status of the individuals is presently unknown.

Adult↗
PubMedDate not supplied

Investigation of hyperkeratotic activity of polybrominated biphenyls in Firemaster FF-1.

A polybrominated biphenyl (PBB) mixture was fractionated by normal-phase preparative high-performance liquid chromatography. The hexane fractions were concentrated and applied to rabbit ears. Only the most polar fraction produced hyperkeratosis on the rabbit ears. This active fraction was subfractionated by using the same procedure. Again, the extent of hyperkeratotic activity increased with increasing polarity. The PBBs of the largest concentration levels in the active fraction were purified by preparative gas chromatography and tested on rabbit ears. The major compounds did not demonstrate hyperkeratotic activity.

Animals↗
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High performance liquid chromatography of mycotoxin metabolites in human urine.

Because mycotoxins occur worldwide in grain and grain products, evaluating their effects on the health of the population has become important. The development of a high performance liquid chromatographic (HPLC) procedure was investigated for the analysis of aflatoxin B1, citrinin, and ochratoxin A, from hydrolyzed human urine. Solid-phase extraction (SPE) was used for sample clean-up and concentration. Reversed-phase liquid chromatography (RPLC) was used with fluorescence detection for sample analysis. The presence of aflatoxin B1 was confirmed by converting it to the hemiacetal. With 10 mL of urine, the detection limit for aflatoxin B1 and ochratoxin A was in the high parts per trillion (ppt) and that for citrinin was about 10 ppb.

Aflatoxin B1↗
PubMedDate not supplied

A comparison of two methods for quantifying D-glucaric acid.

The relative usefulness of two spectrophotometric methods for quantifying urinary D-glucaric acid was evaluated. The enzyme inhibition method measures the inhibition of beta-D-glucuronidase by the 1,4-glucarolactone produced from D-glucaric acid in urine by boiling at acidic pH. The glyoxylic acid method measures glyoxylic acid produced from the oxidation of D-glucaric acid which has first been separated from other urinary compounds by ion exchange chromatography. For a group of 61 healthy adults, the enzyme inhibition method gave a range similar to that of previously reported values: 0 to 6.44 mmol D-glucaric acid/mol creatinine (99% confidence limits). Similar values were obtained from standard solutions by the two methods. Recovery was approximately 105% by both methods. Urinary concentrations, however, were often from 3 to 10 times higher by the glyoxylic acid method. The higher values were probably due to interference from ascorbic acid and other glyoxylic acid-producing compounds, because the reduction of interfering compounds with sodium borohydride before chromatography resulted in concentrations of less than half of those originally observed. It is concluded that the modification of the enzyme inhibition method is preferable because it is less subject to interference and less labor intensive than the glyoxylic acid method.

Chromatography, Ion Exchange↗
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Quantification of selected herbicides and chlorinated phenols in urine by using gas chromatography/mass spectrometry/mass spectrometry.

We have developed a method for determining selected chlorinated phenols and phenoxy herbicides in urine. The process of preparing the samples includes acid hydrolysis, extraction with benzene, derivatization with diazoethane, and column chromatography cleanup. We quantify the more volatile compounds by using capillary column gas chromatography/positive chemical ionization/mass spectrometry/mass spectrometry. Less volatile compounds are quantified by using electron capture negative chemical ionization in a single stage mass spectrometry mode. Quality control samples are included in each analytical run, and the results demonstrate that the analytical system is in control. Positive values for the target analytes are determined on the basis of appropriate relative retention time, a signal-to-noise ratio greater than 3:1, and a calculated concentration greater than 1 ppb. We determine the chlorine isotope ratios for each compound to assess the presence or absence of interferences. This analytical method has been applied in a case-control study of 199 individuals to examine exposure to the 12 target analytes.

Child↗
PubMedDate not supplied

Determination of selected organochlorine pesticides and polychlorinated biphenyls in human serum.

A method is presented that can be used to determine the residue level of certain chlorinated pesticides and polychlorinated biphenyls (as Aroclor 1260) in serum. The method involves the following: (1) extraction of denatured serum with organic solvents; (2) elution of the organic extract through micro-Florisil columns to obtain two fractions; (3) acid treatment of the less polar Florisil fraction and its subsequent elution through deactivated silica gel to obtain two fractions; and (4) analysis of all three fractions using gas-liquid chromatography with electron capture detection. The method produced in vitro recoveries for 10 pesticides spiked in the range of 1-10.7 ppb of 50.4% to 121.6%, and in the range of 4.98-21 ppb, recoveries ranged from 47.7 to 112.6. In vivo "recoveries" of Aroclor 1260 averaged 104.8% and 92.3% for concentration levels of approximately 10 and approximately 30 ppb, respectively. The method could not be compared with the more commonly used hexane extraction technique because of the deleterious effect these extracts had on the gas chromatographic system.

Chemistry Techniques, Analytical↗
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Potential compounds for monitoring method performance in the determination of selected organochlorine pesticides and polychlorinated biphenyls in human serum.

Four compounds--2,2', 3,4'-tetrachlorobiphenyl, decachlorodiphenylether, 1,1-dichloro-2,2-bis(p-ethylphenyl)ethane, and dichlorobenzophenone--are recommended for monitoring the within-sample behavior of an analytical method that quantifies chlorinated pesticides and polychlorinated biphenyls (such as Aroclor 1260) in serum using packed column gas chromatography with electron capture detection. Percent recoveries of these surrogates averaged greater than 80%, except with dichlorobenzophenone, which had an average recovery of greater than 70%.

Antineoplastic Agents↗
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Laboratory investigation of a poisoning epidemic in Sierra Leone.

In June 1986, an epidemic of poisoning occurred in Sierra Leone, West Africa; it involved 49 persons--with 14 deaths. Our laboratory's approach and investigation of this incident is described. Using positive chemical ionization mass spectrometry and nuclear magnetic resonance spectroscopy, the toxicant was identified as parathion, a highly toxic organophosphorus pesticide. Analysis of various items supported the epidemiologic hypothesis that bread was made from contaminated flour and that the flour became contaminated with parathion during a truck shipment. Modern analytical instruments played a major role in this laboratory investigation and effected the identification of the unknown toxicant within hours of receiving the initial bread sample. Close cooperation and clear communication between the epidemiologic and laboratory teams were important in this investigation.

Bread↗
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An improved analysis for chlorinated pesticides and polychlorinated biphenyls (PCBs) in human and bovine sera using solid-phase extraction.

Chlorinated pesticides and polychlorinated biphenyls (PCBs) remain public health concerns because of their unresolved health impact and their persistence in humans. Current epidemiological studies of cancer, non-Hodgkins lymphoma, and endocrine disruption in National Center for Environmental Health (NCEH) laboratories require exposure assessment of many analytes in thousands of people. Previous methods of analyzing pesticides and PCBs in serum have proven inadequate for timely processing of the number of samples required for epidemiological studies. A new method that involves solid-phase extraction (SPE) and cleanup followed by dual-column gas chromatographic separation and electron capture detection has been developed. Nine surrogate compounds were added to the serum prior to sample workup to provide quality assurance for the SPE steps. These surrogates mimic the chemistry of the analytes in the extraction, cleanup, and gas chromatographic analysis steps. To increase selectivity, extracts were injected onto two gas chromatographs with different capillary columns, a DB-1701 and a DB-5. Recoveries of 17 pesticides, 28 PCB congeners, and one polybrominated biphenyl congener ranged from 40 to 80%. Recoveries from this procedure were found to be similar to those from the previously used liquid-liquid extraction method. Correlation of analyte and surrogate recoveries were compared to examine the ruggedness of the technique. The SPE method was found to provide improved sample throughput by a factor of 15.

Animals↗
PubMedDate not supplied

Interlaboratory comparison for results of analyses for polybrominated biphenyls in human serum.

Four hundred and sixty-six "blind" duplicate serum samples were analyzed for polybrominated biphenyls (PBB) by gas chromatography in two laboratories. As calculated by the regression model of Deming, the correlation coefficient for these 466 samples, whose values ranged from nondetectable amount to 1240 parts per billion was 0.9983. Prior to these analyses, the method was validated in both laboratories by using in vitro and in vivo PBB serum pools.

Chromatography, Gas↗
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Determining pentachlorophenol in body fluids by gas chromatography after acetylation.

A sensitive, precise, and accurate method for rapidly analyzing body fluids for pentachlorophenol has been developed. The method includes acidification and extraction of the fluid with hexane. The extract is reacted with acetic anhydride, washed with buffer, and injected into a gas chromatograph fitted with an electron capture detector. Quantitation of the pentachlorophenol is based on the ratio of the peak height of pentachlorophenyl acetate to an internal standard, tribromophenyl acetate. The lower detection limit in urine or serum is 1-2 parts per billion. The method was applied to workers in pentachlorophenol formulating plants and to residents of pentachlorophenol treated log houses. Hydrolysis increased the yield of determined urinary pentachlorophenol by a factor of approximately 1.8. Serum levels of pentachlorophenol were 2-3 time higher than the corresponding whole blood levels.

Acetylation↗
PubMedDate not supplied

Determination of 19 chlorophenols by packed-column gas chromatography.

The use of packed columns has been explored for the gas chromatographic separation and identification of all 19 chlorophenol congeners after acetylation. Numerous mixtures of polar or nonpolar packings with either of two commercial Bentone 34 mixtures were tested. A mixture of 5% OV-101, 1.75% Bentone 34 on Chrom W-HP (100/120) mixed with twice its weight of 3% OV-225 on 100/120 Supelcoport separated all 19 congeners.

Chlorophenols↗