James S. Holler

Residues of chlorinated phenols and phenoxy acid herbicides in the urine of Arkansas children.

Urine samples from 197 Arkansas children were analyzed for eight chlorinated phenols and four chlorinated phenoxy herbicides by using a new procedure that combined gas chromatography with tandem mass spectrometry. With the detection limit of 1 part per billion (ppb), six of these pesticides were detected in more than 10% of the samples. 2,5-Dichlorophenol (a metabolite ofp-dichlorobenzene), and pentachlorophenol were detected in 96% and 100%, respectively, of the childrens urine at median concentrations of 9 ppb and 14 ppb, respectively. 2,4,5-Trichlorophenol was detected in 54% of the childrens urine at a median concentration of 1 ppb. One trichlorophenol and three other dichlorophenols were found in 3% to 27% of the samples. The herbicide 2,4-dichlorophenoxyacetic acid was observed in 20% of all samples. The concentrations of all analytes are reported as background or reference levels for use in future studies. The finding of 2,5-dichlorophenol as a ubiquitous contaminant merits further study.

Human adipose data for 2,3,7,8-tetrachlorodibenzo-p-dioxin in certain U.S. samples

Abstract We report the results of analyses of human adipose from 35 autopsy cases from Georgia and Utah for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). We also report the effect of storing the samples and our quality control plan. The geometric mean of values for 2,3,7,8-TCDD in these samples on a whole-weight basis was 7.1 ppt. The geometric mean of values for 2,3,7,8-TCDD in 31 of these samples on a lipid basis was 9.6 ppt.

Dioxin and Dioxin-Like Compounds in Soil, Part I: ATSDR Interim Policy Guideline

1. Address all correspondence to: Christopher T. De Rosa, Ph.D., Director, Division of Toxicology, Agency for Toxic Substances and Disease Registry, Mailstop E-29, 1600 Clifton Road, NE, Atlanta, GA 30333. Tel.:(404)639-6300. Fax:(404)639-6315. E-mail:cyd0@cdc.gov. 2. Abbreviations: ATSDR, Agency for Toxic Substances and Disease Registry; CDDs, chlorinated dibenzop-dioxins; CDFs, chlorinated dibenzofurans; CERCLA, Comprehensive Environmental Response, Compensation, and Liability Act of 1980; EMEG, environmental media evaluation guide; FDA, U.S. Food and Drug Administration; MRL, minimal risk level; TCDD, 2,3,7,8-tetrachlorodibenzo-dioxin; TEF, toxicity equivalency factor; TEQs, toxicity equivalents. 3.

Safe handling of chemical toxicants and control of interferences in human-tissue analysis for dioxins and furans

The development of a comprehensive analytical program in ultratrace analyses of toxic substances requires a facility specifically devoted to synthesis activities and for making analytical standards. The development of adequate operational procedures for such a facility is described. Environmental monitoring is a key activity in protecting the laboratory worker and the analytical integrity of ongoing studies. A wipe test procedure is described that provides the information needed to pinpoint sources of contamination. Examples of operational problems and remedial actions are described for the development of a parts per trillion dioxin analytical method. 8 references, 4 figures, 3 tables.

Site-specific consultation for a chemical mixture

The Agency for Toxic Substances and Disease Registry (ATSDR) uses the weight of evidence methodology to evaluate interactions of chemical mixtures. In the process, toxicity, toxicokinetics, and toxicodynamics of chemical components of the mixture are carefully examined. Based on the evaluation, predictions are made that can be used in real-life situations at hazardous waste sites. In this paper, health outcomes were evaluated for a mixture of eight compounds that were found at a specific site. These eight chemicals were identified and possibly associated with human exposure. The health assessors could consider similar thought processes when evaluating chemical mixtures at hazardous waste sites.

Problems associated with interferences in the analysis of serum for polychlorinated biphenyls

During a recent survey to determine serum concentrations of polychlorinated biphenyls (PCBs) among people living around New Bedford, MA, U.S.A., an unidentified contaminant precluded the quantification of some early eluting Webb and McCall peaks. Loss of data is estimated to have reduced reported serum levels by 12%. Efforts to identify the contaminant by gas chromatography with an electron-capture detector, a Hall electrolytic condutivity detector, and mass spectrometer were not successful. Researchers ascertained, however, that the contaminant is not a PCB, it does not contain halogens, but it may contain phthalates. Vacutainer tubes and closures for serum storage bottles are suspected sources of contamination.

Determining Priority Hazardous Substances Related To Hazardous Waste Sites

1. Address all correspondence to: Nickolette Roney, MPH, Agency for Toxic Substances and Disease Registry, Division of Toxicology, 1600 Clifton Road, Mailstop E29, Atlanta, GA . 30333. Tel.:(404) 639-5292. Fax:(404) 639-6315. E-mail:nxr6@cdc.gov. 2. Abbreviations: ATSDR, Agency for Toxic Substances and Disease Registry; CERCLA, Comprehensive Environmental Response, and Liability Act; SARA, Superfund Amendments and Reauthorization Act; NPL, National Priorities List; HazDat, Hazardous Substance Release/Health Effects database; RQ, Reportable Quantity; TES, Toxicity/Environmental Score; SC, Source Contribution. 3.

Reducing uncertainty in the derivation and application of health guidance values in public health practice. Dioxin as a case study.

Abstract: We were requested by the U.S. Environmental Protection Agency (EPA) to clarify the relationships among the minimal risk level (MRL), action level, and environmental media evaluation guide (EMEG) for dioxin established by the Agency for Toxic Substances and Disease Registry (ATSDR). In response we developed a document entitled “Dioxin and Dioxin‐Like Compounds in Soil, Part I: ATSDR Interim Policy Guideline”; and a supporting document entitled “Dioxin and Dioxin‐Like Compounds in Soil, Part II: Technical Support Document”. In these documents, we evaluated the key assumptions underlying the development and use of the ATSDR action level, MRL, and EMEG for dioxin. We described the chronology of events outlining these different health guidance values for dioxin and identified the areas of uncertainty surrounding these values. Four scientific assumptions were found to have had a great impact on this process; these were: (1) the specific uncertainty factors used, (2) the toxicity equivalent (TEQ) approach, (3) the fractional exposure from different pathways, and (4) the use of body burdens in the absence of exposure data. This information was subsequently used to develop a framework for reducing the uncertainties in public health risk assessment associated with exposure to other chemical contaminants in the environment. Within this framework are a number of future directions for reducing uncertainty, including physiologically based pharmacokinetic modeling (PBPK), benchmark dose modeling (BMD), functional toxicology, and the assessment of chemical mixture interactions.

Halogenated aromatic hydrocarbons and toxicity equivalency factors (TEFs) from the public health assessment perspective

The validity of the toxicity equivalency factors (TEFs) approach to predicting toxicity of mixtures was investigated on the basis of the public health risk assessment that had been posted for different groups of halogenated aromatic hydrocarbons. First, the minimal risk levels (MRLs) were derived based on the databases available for chlorinated dibenzo-p-dioxins (CDDs), chlorinated dibenzofurans (CDFs), and polychlorinated biphenyls (PCBs). The MRL values were then converted to 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) toxicity equivalents (TEQs) and compared with each other. There was a good correlation between intermediate duration oral MRLs for TCDD and 2,3,4,7,8-pentaCDF when expressed in TEQs (7 pg/kg/day and 15 pg/kg/day). Although the studies that served for derivation of these MRLs used different species (guinea pigs and rats, respectively), the toxicity endpoints (immunological and hepatic for TCDD and hepatic for 2,3,4,7,8-pentaCDF) were comparable. The hepatic effects were measured by the same techniques (blood chemistry and histopathology), ensuring similar sensitivity. However, there was a discrepancy between acute oral MRLs for TCDD and 2,3,4,7,8-pentaCDF when they were expressed in TEQs (20 pg/kg/day and 500 pg/kg/day, respectively). The studies used for MRL derivation involved not only different species (mice and guinea pigs, respectively), the immunotoxicity endpoints were measured by techniques with different sensitivity (serum complement activity versus histopathology), making comparison difficult. Further calculations showed that the TEFs approach may be feasible for individual coplanar congeners of PCBs, but not for a mixture of Aroclors. Correlations presented here support the concept that the TEFs are valid only if specific criteria for their derivation are met (e.g., a broad database of information, consistency across endpoints, additivity for the effects, a common mechanism of action, etc.). In environmental exposure, the total toxicity of halogenated aromatic hydrocarbons is not necessarily the sum of the total individual congener toxicities because individual congeners compete for the same receptor; therefore, nonadditive behavior may occur.

Prospective trends in quantitative mass spectrometry

Solving most analytical problems requires information about the identity of compounds in a sample and some estimate of the amounts. Mass spectrometry, alone and in combination with chromatographic techniques, often provides the most satisfactory quantitative answer in terms of specificity and sensitivity. Monitoring human populations with exposure to elevated levels of toxic chemicals illustrates the type of analytical problem the chemist can solve by using existing technologies. Gas chromatography/mass spectrometry is the best method for measuring the extent of environmental contamination from toxic waste sites. Mass spectral methods are often used in regulatory situations to validate routine analytical methods for biomedical measurement. Measuring isotope ratios by mass spectrometry can provide information on the origins of certain compounds, as demonstrated in tracer studies for inorganic elements and for the determination of adulteration for several natural products. These analytical techniques will become more important in quantitative studies. New, low cost mass spectrometers and computerized data systems will be used in routine studies, and developments in chromatographic interface technology will facilitate specialized instrument systems designed for particular applications. A hope for future technological development is improved source design, with increased sensitivity and the ability to use samples more efficiently.