Agency For Toxic Substances And Disease Registry Research Articles

Erratum: "A Biomonitoring Study of Lead, Cadmium, and Mercury in the Blood of New York City Adults".

[This corrects the article DOI: 10.1289/ehp.10056.].

Physiologically based pharmacokinetic (PBPK) tool kit for environmental pollutants – metals

The Agency for Toxic Substances and Disease Registry (ATSDR) is mandated by the US Congress to identify significant human exposure levels, develop methods to determine such exposures, and design strategies to mitigate them. Physiologically based pharmacokinetic (PBPK) models are increasingly being used to evaluate toxicity of environmental pollutants through multiple exposure pathways. As part of its translational research project, ATSDR is developing a human ‘PBPK model tool kit’ that consists of a series of published models re-coded in a common simulation language. The tool kit currently consists of models, at various stages of development, for priority environmental contaminants including solvents and persistent organic pollutants. Presented here are results of translational activities of re-coding models for cadmium, mercury, and arsenic. As part of this work, following re-coding each new model was evaluated for fidelity followed by sensitivity analysis. Good agreement was generally obtained for all three models when predictions of original and re-coded model simulations were compared. Also presented is an application of the cadmium toxicokinetic model to interpret biomonitoring data from the National Health and Nutrition Examination Survey (NHANES). The PBPK tool kit will enable ATSDR scientists to perform simulations of exposures from contaminated environmental media at sites of concern and to better interpret site-specific biomonitoring data.

Targeted Therapies Take Aim Against Lung Cancer and Melanoma

More than 300 staff from the Centers for Disease Control and Prevention (CDC) and the Agency for Toxic Substance and Disease Registry (ATSDR) are monitoring health threats from the oil spill in five Gulf states through the National Poison Data System, which has taken 651 calls related to exposure to the oil spill as of July 8, and BioSense, which reports that there have been no increases in specific syndromes at 86 coastal health care facilities. The CDC’s National Institute for Occupational Safety and Health (NIOSH) is providing technical assistance in training clean-up workers, creating rosters of workers to track them for illnesses later if necessary, and coordinating the collection of analysis of injury and illness data BP is required to report. CDC is also reviewing the results of the EPA’s daily environmental samples to determine whether the level of detected pollutants constitutes a health hazard. BP has pledged $500 million to the Gulf of Mexico Research Initiative to study the impact of the spill on the environment and public health. And the National Institutes of Health announced it will devote $10 million to support research on potential human health effects. Research and surveillance can’t start soon enough, stressed John C. Bailar III, MD, PhD, professor emeritus in the Department of Health Studies at the University of Chicago. “Every day matters. People will move away, memories will fade or change, and environmental samples will be altered with the passage of time.” Also crucial, Bailar said, is for a single organization to direct the research efforts “so that all the data can be assembled to tell a convincing story.” And research needs to be coordinated locally, said Maureen Y. Lichtveld, MD, MPH, professor and chair of the department of environmental health sciences at Tulane University School of Public Health and Tropical Medicine. “What we don’t need, frankly, is a repeat of Hurricane Katrina where researchers descended on New Orleans and did all sorts of studies, but the community was left without the answers it needed. We need meaningful data that will let communities take the next steps.”

Interpreting REACH guidance in the determination of the derived no effect level (DNEL)

Under the new European chemicals regulation, REACH, a new safety value, the Derived No Effect Level (DNEL) must be established for all chemicals manufactured, imported or used in the EU in quantities greater than 10 metric tonnes per year. The DNEL is to be calculated for all relevant exposure pathways, exposure populations, and endpoints of toxicity. The EU has published guidance on how to derive the DNEL, but this guidance has yet to be put into practice and is in some places not prescriptive. Using the Agency for Toxic Substances and Disease Registry (ATSDR) dataset, we have determined inhalation DNELs for styrene. In doing so, we considered what effect key decisions would have on the calculated DNEL. The resulting DNELs were then compared to existing risk criteria values or occupational exposure limits. General population DNELs were generally more conservative than analogous risk criteria (ranging from approximately 0.05 to 2.5 ppm). Worker DNELs are lower than existing occupational standards (ranging from approximately 0.4 to 20 ppm). To our knowledge, this work represents the first rigorous application and interpretation of the EU guidance for determination of a DNEL and will prove useful as a model for determination of other DNELs under REACH.

Biomonitoring equivalents for hexachlorobenzene

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline. This study reviews available health-based exposure guidance values for hexachlorobenzene (HCB) from Health Canada, the United States Environmental Protection Agency (US EPA), the US Agency for Toxic Substances and Disease Registry (ATSDR) and World Health Organization (WHO). HCB liver tissue concentrations in chronic rodent bioassays and information on human elimination rates and tissue distribution of HCB were extrapolated to estimate serum lipid-adjusted HCB concentrations that are consistent with the exposure guidance values for HCB. Estimated serum lipid-adjusted HCB concentrations ranging from 16 to 250 ng/g lipid were consistent with non-cancer-based exposure guidance values from various agencies. Concentrations associated with cancer risk-specific doses at target risk levels of interest were also estimated. These BE values may be used as screening tools for evaluation of population biomonitoring data for HCB in a risk assessment context and can assist in prioritization of the potential need for additional risk assessment efforts for HCB relative to other chemicals.

Biomonitoring Equivalents for inorganic arsenic

This paper presents Biomonitoring Equivalents (BEs) for inorganic arsenic. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for arsenic based on recent evaluations from the United States Environmental Protection Agency (US EPA), US Agency for Toxic Substances and Disease Registry (ATSDR) and Health Canada (HC). BE values corresponding to the Reference Dose (RfD) or risk-specific doses for cancer endpoints from these agencies were derived based on kinetic data (urinary excretion) from controlled dosing studies in humans. The BE values presented here provide estimates of the sum of inorganic arsenic-derived urinary biomarkers (inorganic arsenic, monomethylated arsenic, and dimethylated arsenic). The BE associated with the United States Environmental Protection Agency’s Reference Dose and the Agency for Toxic Substances and Disease Registry’s Minimal Risk Level is 6.4 μg arsenic/L urine. The BEs associated with the various cancer risk assessments are significantly lower. These BE values may be used as screening tools for evaluation of biomonitoring data for inorganic arsenic in a public health risk context.

Levels of polycyclic aromatic hydrocarbons (PAHs) in the Densu River Basin of Ghana

The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in Densu River Basin in Ghana were measured using gas chromatograph. Surface water samples were collected from nine stations, namely, Potroase, Koforidua Intake, Suhyien, Mangoase, Asuboi, Nsawam Bridge, Afuaman, Ashalaga, and Weija Intake in the Densu Basin. Total PAH concentrations varied from 13.0 to 80.0 μg/mL in the Densu River, with a mean value of 37.1 μg/mL. The two- to three-ring PAHs (low-molecular-weight PAHs) were found to be dominant in the Densu River Basin. Total PAH concentrations showed the following pattern: Koforidua Intake (80.0 μg/mL) > Asuboi (50.8 μg/mL) > Afuaman (47.9 μg/mL) > Weija Intake (45.0 μg/mL) > Suhyien (27.6 μg/mL) > Nsawam (23.5 μg/mL) > Ashalaja (22.9 μg/mL) > Potroase (23.3 μg/mL) > Mangoase (13.0 μg/mL). According to the Agency for Toxic Substances and Disease Registry (ATSDR), background levels of PAHs in drinking water supplies in the USA range from 0.004 to 0.024 μg/mL. PAH levels from all sites exceeded the range set by ATSDR. B[a]P contributed the highest carcinogenic exposure equivalent (0.3 μg/mL), followed by B[a]A (0.132 μg/mL) and B[b]F (0.08 μg/mL), contributing 52.6%, 23.2%, and 4.6%, respectively, of the total carcinogenicity of surface water PAH in the Densu River Basin. The carcinogenic potency was estimated to be 0.57 μg/mL. The presence of PAHs was an indication of the water sources being contaminated, with potential health implications.

Assessment of dioxin-like soil contamination in Mexico by enzyme-linked immunosorbent assay.

In this work, we describe the results of a preliminary soil assessment program for the detection of dioxins at different sites in Mexico performed by immunoassay. We studied five different sectors considered relevant sources of dioxins: Anaversa and Tekchem industrial areas where organochlorine pesticides were manufactured and released by accidental explosions, secondary smelters, brick kilns, and rural dwellings. In the context of the Agency for Toxic Substances and Disease Registry (ATSDR) guidelines, only the brick kilns sites can be considered as low-risk areas. The dioxin concentrations detected in the vicinity of the Anaversa and Tekchem chemical plants and secondary smelters exceed the screening level of 0.05 ppb set by the ATSDR, and therefore further site-specific studies are needed. The dioxin levels found in all soot samples from indigenous dwellings where wood is used for indoor cooking were above the evaluation level. Considering that the studied areas are representative examples of dioxin sources in less developed countries, our work demonstrates the useful application of dioxin immunoassays as a tool for dioxin screening for environmental assessment programs in developing countries.

Chemical risk assessment and uncertainty associated with extrapolation across exposure duration

The Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on priority substances in which available epidemiologic and toxicologic data are reviewed, summarized, and interpreted. When adequate data are available, ATSDR derives health guidance values called minimal risk levels (MRLs) for acute, intermediate, and chronic durations of exposure for oral and inhalation routes of exposure. The MRLs are generally derived by use of the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level/uncertainty factor (LOAEL/UF) approach. The UF usually employed are for LOAEL-to-NOAEL extrapolation, animal to -human extrapolation, and inter-human variability. These health guidance values are intended to serve as screening tools for health assessors and other responders to identify contaminants of concern and potential health effects in the community at hazardous waste sites and during unplanned releases. When guidance values are not available for a specific exposure scenario because of a lack of chronic data, extrapolation across exposure durations may be made. For example, chronic guidance values may be derived from subchronic data by applying an additional uncertainty factor of 10 for extrapolation to chronic exposure duration. In this paper, we analyzed the ratio of chemical-specific LOAELs from acute to intermediate and from intermediate to chronic durations for oral and inhalation exposure routes. In addition, we investigated the impact of chemical structure and chemical structure activity relationship on validation of predictions across exposure durations.

Derivation of Biomonitoring Equivalents for di- n-butyl phthalate (DBP), benzylbutyl phthalate (BzBP), and diethyl phthalate (DEP)

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for di- n-butyl phthalate (DBP), benzylbutyl phthalate (BzBP), and diethyl phthalate (DEP) from Health Canada, the United States Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR), and the European Food Safety Authority (EFSA). BE values corresponding to the oral reference dose (RfD), minimal risk level (MRL) or tolerable daily intake (TDI) estimates from these agencies were derived for each compound based on data on excretion fractions of key urinary metabolites. These values may be used as screening tools for evaluation of biomonitoring data for metabolites of these three phthalate compounds in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for each of these compounds relative to other chemicals.

Derivation of Biomonitoring Equivalents for di(2-ethylhexyl)phthalate (CAS No. 117-81-7)

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of an environmental chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for di(2-ethylhexyl)phthalate (DEHP) from Health Canada, the United States Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR), the European Chemicals Bureau (ECB), and the European Food Safety Authority (EFSA). BE values corresponding to the oral reference dose (RfD), minimal risk level (MRL) or tolerable daily intake (TDI) estimates from these agencies were derived based on data on excretion fractions of key urinary metabolites. BE values based on the sum of three, four, and five of the most predominant and commonly-measured metabolites of DEHP are presented. These values may be used as screening tools for evaluation of biomonitoring data for DEHP metabolites in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for DEHP relative to other chemicals.

Commentary: Improving Community Health: Brownfields and Health Monitoring

This commentary highlights efforts to promote health moni­ toring in brownfields communities. Both the Agency for Toxic Substances and Disease Registry (ATSDR) and the United States Environmental Protection Agency (US EPA) recognize how public health may be improved by including a holistic approach to redevelopment that includes community health monitoring activities. Health monitoring goes beyond testing blood samples to address potentially toxic exposures and can be implemented to assess overall community health status throughout the course of community revitalization efforts. Examples of health monitoring activities include asthma or blood lead level screening, reviewing health statistics, envi­ ronmental testing, and evaluation of community-specific health concerns. While health monitoring is encouraged as an ac­ tivity within US EPA Brownfields funding, the number of communities that implement health monitoring programs is low. To encourage more communities to implement health monitoring activities, with or without Brownfields funding, this paper describes several projects by health agencies and communities to represent best practice examples. To facili­ tate more community health monitoring projects, the ATSDR has created and continues to create tools and resources to assist brownfield and land-reuse communities. In addition, the ATSDR and the US EPA are working together to build internal as well as community capacity to monitor commu­ nity health through redevelopment activities. Environmental Practice 11:190–195 (2009)

Levels of arsenic in human hair as biomarkers of arsenic exposure in a mining community in Ghana

Arsenic levels were determined in human hair samples collected from a mining and non-mining community in Ghana. Hair samples were digested and analyzed using inductively coupled plasma atomic emission spectrometer (ICP–AES). Elevated levels of arsenic were found in the samples obtained from the mining community, the mean levels in the hair ranged from 0.0142–0.0515 μg/g, whereas arsenic was not detected in the hair samples from the non-mining community. The values obtained from the mining community were all below background levels set by the Agency for Toxic Substance and Disease Registry (ATSDR). The results therefore indicate that arsenic pollution may indeed be associated with mining, inducing human environmental exposure.

Making the Needed Linkages and Economic Case for Continued Lead-Paint Abatement

Making the Needed Linkages and Economic Case for Continued Lead-Paint Abatement

Impact of Gold Mining on Soil and some Staple Foods Collected from Selected mining communities in and around Tarkwa-Prestea Area

The principle of neutron activation was used to investigate the presence of toxic elements and possible heavy metals in samples of cassava, plantain and soil from the mining communities in and around Tarkwa in the Western Region of Ghana. The results showed that the maximum concentrations of the respective metals in cassava: plantain: soil samples were arsenic (As = 0.7 ƒÊg/g:0.25 ƒÊg/g:14.35 ƒÊg/g), mercury (Hg = 0.25 ƒÊg/g:0.52 ƒÊg/g:0.09 ƒÊg/g), antimony (Sb = 0.03 ƒÊg/g: 0.03 ƒÊg/g: 2.98 ƒÊg/g ), chromium (Cr = 0.72 ƒÊg/g:3.42 ƒÊg/g:40.35 ƒÊg/g ), vanadium (V = 0.8 ƒÊg/g:0.76 ƒÊg/g:188.40 ƒÊg/g ), zinc (Zn = 38.42 ƒÊg/g:24.92 ƒÊg/g:42.36 ƒÊg/g), and copper (Cu = 66.39 ƒÊg/g: 8.74 ƒÊg/g: 53.46 ƒÊg/g). The concentrations in cassava and plantain were higher than the values proposed by the FAO, the Expert Committee on Food Additives of the WHO and the Agency for Toxic Substance and Disease Registry (ATSDR). The concentrations of Hg (0,09 ƒÊg/g) in soil at Teberebie and of V (188.40ig/g) at the University of Mines and Technology (UMaT) in soil were above the permitted concentrations of 5 ƒÊg/g and 90 ƒÊg/g, respectively. Samples from communities further away from the centres of mine drainages (mile 8., mile 10.) had smaller values of element concentrations. An enrichment factor (EF) analysis for both cassava and plantain were Zn (7%) and Hg (90%). The remaining elements together add up to 3%. The enrichment factor analysis for plantain is greater than that for cassava. Mercury is the element that is chiefly enriched in both cassava and plantain. The second predominant element enriched in cassava and plantain is zinc.

Binary weight-of-evidence evaluations of chemical interactions—15 years of experience

The paper reflects on the last 15 years of experience in the field of mixtures risk assessment. It summarizes results found in various documents developed by the Agency for Toxic Substances and Disease Registry (ATSDR) of the weight-of-evidence (WOE) approach applied to 380 binary combinations of chemicals. Of these evaluations, 156 assessments indicated possible additivity of effects [=], 76 indicated synergism (greater-than-additive effects [>]), and 57 indicated antagonism (less-than-additive effects [<]). However, 91 combinations lacked the minimum information needed for making any assessments and, hence, were undetermined. The paper provides examples of the rationale behind some of the WOE decisions and discusses the importance of expert judgments in risk assessment evaluations. Examples are given regarding the importance of human variability in mixtures’ ability to affect human health and regarding the dose versus effect relationships.

AN OBSCURE AGENCY UNDER FIRE

ALTHOUGH FEW PEOPLE have ever heard of the Agency for Toxic Substances & Disease Registry (ATSDR), the relatively obscure sister agency of the Centers for Disease Control & Prevention (CDC) has the...

Reconstructing Historical Exposures to Volatile Organic Compound-Contaminated Drinking Water at a U.S. Military Base

Two of three water-distribution systems that have historically supplied drinking water to family housing at U.S. Marine Corps Base Camp Lejeune, North Carolina, were contaminated with volatile organic compounds (VOCs). Scientific data relating to the harmful effects of VOCs on a child or fetus are limited. Therefore, the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) is conducting an epidemiological study to evaluate potential associations between in utero and infant (up to 1 year of age) exposures to VOCs in contaminated drinking water at Camp Lejeune and specific birth defects and childhood cancers. The study includes births that occurred during the period 1968–1985 to women who were pregnant while they resided in family housing at Camp Lejeune. To support the epidemiological study, water-modeling techniques are being used to reconstruct historical conditions of groundwater flow, contaminant fate and transport, and the distribution of drinking water contaminated with VOCs. Results for this phase of the study indicate that PCE concentrations in drinking water, delivered to the Tarawa Terrace housing area, exceeded the current maximum contaminant level for PCE of 5 micrograms per liter (μg/L) for 346 months—November 1957–February 1987; the maximum simulated PCE concentration in Tarawa Terrace drinking water was 183 μg/L during March 1984 compared to a measured concentration of 215 μg/L during February 1985.

Insights into the Evolution of Environmental Health

<i>Insights</i> into the Evolution of Environmental Health

Derivation of Biomonitoring Equivalent (BE) Values for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds: A Screening Tool for Interpretation of Biomonitoring Data in a Risk Assessment Context

Recent efforts by the U.S. Centers for Disease Control and Prevention and other researchers have resulted in a growing database of measured concentrations of dioxins and related compounds in blood samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring equivalent (BE) values are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments This study reviews available health based exposure guidance values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds from a variety of agencies including the World Health Organization Joint Expert Committee on Food Additives (JECFA), the European Commission Scientific Committee on Foods (ECSCF), the United Kingdom Committee on Toxicology (UKCOT), and the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) to estimate corresponding BE values for dioxin-like compounds in blood on a serum lipid-adjusted basis. Based on data from the animal studies underlying the exposure guidance values, a serum lipid-adjusted dioxin toxicity equivalent (TEQ) concentration of approximately 15 ppt is consistent with the ATSDR minimal risk level (MRL) for dioxins. Serum lipid-adjusted TEQ concentrations of approximately 31 to 74 ppt are consistent with the tolerable intakes estimated by the other three agencies. These values may be used as screening tools for evaluation of biomonitoring data for dioxins in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for dioxins.