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PubMed2004

Validating sample preservation techniques and holding times for the approved compliance monitoring methods for haloacetic acids under the US EPA's stage 1 D/DBP rule.

Haloacetic acids (HAAs), which are formed during the disinfection of drinking waters with chlorine, are regulated by the US Environmental Protection Agency (EPA) under the Stage 1 Disinfectant/Disinfection Byproducts (D/DBP) Rule. Recently, three studies have been reported indicating that low concentrations of HAAs can also be formed during disinfection with chloramines. Methods currently approved for compliance monitoring under the Stage 1 Rule arrest the chlorine-mediated formation of HAAs by adding ammonium chloride, which forms chloramines. Studies were undertaken using an in-process water that favored the formation of HAAs with moderate total organic carbon concentration and high levels of chlorine to investigate the potential formation of HAAs under sample storage conditions. The ammonium chloride-quenched sample did form a small amount of HAAs, but total formation over a period equal to the 14-day sample storage time was less than 2 microg/l, whereas the unquenched samples increased 41 microg/l during the same period. Pour plate studies indicated that chlorinated drinking waters quenched with ammonium chloride are protected from microbial growth, which is an important additional advantage to this preservation scheme. The presence of a combined chlorine residual should prevent microbial degradation of HAAs in samples. These studies support the preservation protocols and the sample storage times promulgated for compliance monitoring under the Stage 1 D/DBP Rule.

Acetic Acid↗
PubMed2005

Treated wood preservatives linked to aquatic damage, human illness, and death--a societal problem.

On February 12, 2002, the US Environmental Protection Agency (EPA) announced a voluntary decision by industry to move consumer use of treated lumber products away from a variety of pressure-treated wood that contains arsenate (As) by December 31, 2003, in favor of new alternative wood preservatives. Chromated copper arsenate (CCA) is a chemical mixture consisting of three pesticidal compounds (As, chromium, and copper) registered for wood preservative uses. CCA is injected into wood by a process that uses high pressure to saturate wood products with the chemical. Only people who have received the proper safety training should use CCA to treat wood products. Around the home, CCA-treated wood is commonly used for decks, walkways, fences, gazebos, boat docks, and playground equipment. Other common uses of CCA-treated wood include highway noise barriers, sign posts, utility posts, and retaining walls. As of January 1, 2004, the EPA is no longer allowing CCA products to be used to treat wood intended for any of these residential uses. This decision will facilitate the voluntary transition to new alternative wood preservatives that do not contain As in both the manufacturing and retail sectors. To its credit, the EPA has developed consumer safety information sheets, hanging signs, end signs, and bin stickers that provide comprehensive information about the dangers of CCA-treated wood, use-site, and handling precautions. The EPA has not concluded that CCA-treated wood poses any unreasonable risk to the public or the environment. Nevertheless, As is a known human carcinogen and, thus, the EPA believes that any reduction in the levels of potential exposure to As is desirable. The toxicologic manifestations have been primarily related to the effects of As exposure from drinking water sources and include the following: acute poisoning incidents, cardiovascular effects, diabetes mellitus, and cancer. Understanding the biomethylation of As is central to elucidating its action as a toxin and a carcinogen. In humans as in many other species, inorganic As is enzymatically converted to the methylated products methyl As (MAs) and dimethyl As (DMAs). The aforementioned voluntary agreement to reduce the uses of CCA-treated wood does not include a ban on the use of CCA for residential roofing. A major reason that this wood product should be banned from residential roofing is that it does not provide a Class "A" fire-rated roof system, which markedly reduce the frequency of residential roof fires.

Arsenic Poisoning↗
PubMed2004

Effects of pyrethroids on voltage-sensitive calcium channels: a critical evaluation of strengths, weaknesses, data needs, and relationship to assessment of cumulative neurotoxicity.

The Food Quality Protection Act of 1996 requires that the U.S. Environmental Protection Agency conduct cumulative risk assessments for classes of pesticides that have a common mode or mechanism of action. For the pyrethroid insecticides, disruption of voltage-sensitive sodium channel function is generally accepted as the mechanism underlying acute neurotoxicity. However, data exist which suggest that voltage-sensitive calcium (Ca(2+)) channels (VSCC) may also be important targets of pyrethroid action. VSCC are important to neuronal function during development and for neurotransmitter release, gene expression, and electrical excitability in the nervous system. Disruption of these and other processes mediated by VSCC can result in neurotoxicity. If effects on VSCC are demonstrated to contribute to pyrethroid neurotoxicity, then such effects will have to be considered when making decisions regarding cumulative risk of exposure to this class of compounds. This document provides a critical review of the data related to the hypothesis that VSCC are important targets of pyrethroid effects. Data supporting effects of pyrethroids on VSCC have been generated by several different laboratories using different techniques and biological preparations. Thus, the many reports of effects on VSCC provide evidence that pyrethroids may interact with VSCC. However, evidence to support a role of VSCC in pyrethroid neurotoxicity is based entirely on in vitro observations, and numerous limitations exist in these data, including: (1) lack of defined concentration-response relationships, with some effects observed only at relatively high concentrations, (2) the use of indirect measures of VSCC function, (3) data from nonmammalian species, (4) data from studies that have not been peer-reviewed, (5) the need for replication of some effects, and (6) inconsistent or contradictory results from different laboratories/preparations. Thus, at the present time, it is premature to conclude that effects on VSCC play an important role in the acute neurotoxicity of pyrethroid insecticides in mammals. To demonstrate that VSCC are important targets of pyrethroid neurotoxicity in mammals, in vivo studies supporting a role for pyrethroid effects on VSCC are needed. Additional support could be provided by demonstration of direct effects of pyrethroid compounds on mammalian neuronal VSCC in vitro, including demonstration that concentration-response relationships are similar, or greater, in sensitivity to effects of pyrethroids on voltage-sensitive sodium channels. If such effects were to be demonstrated, the rationale for considering VSCC as targets of pyrethroid compounds when assessing cumulative risk would be strengthened. However, at the present time, the data available neither support nor refute conclusively the hypothesis that effects on VSCC are important to the acute neurotoxicity of pyrethroids.

Animals↗
PubMed1996

The linearized multistage model and the future of quantitative risk assessment.

The linearized multistage (LMS) model has for over 15 years been the default dose-response model used by the U.S. Environmental Protection Agency (USEPA) and other federal and state regulatory agencies in the United States for calculating quantitative estimates of low-dose carcinogenic risks from animal data. The LMS model is in essence a flexible statistical model that can describe both linear and non-linear dose-response patterns, and that produces an upper confidence bound on the linear low-dose slope of the dose-response curve. Unlike its namesake, the Armitage-Doll multistage model, the parameters of the LMS do not correspond to actual physiological phenomena. Thus the LMS is 'biological' only to the extent that the true biological dose response is linear at low dose and that low-dose slope is reflected in the experimental data. If the true dose response is non-linear the LMS upper bound may overestimate the true risk by many orders of magnitude. However, competing low-dose extrapolation models, including those derived from 'biologically-based models' that are capable of incorporating additional biological information, have not shown evidence to date of being able to produce quantitative estimates of low-dose risks that are any more accurate than those obtained from the LMS model. Further, even if these attempts were successful, the extent to which more accurate estimates of low-dose risks in a test animal species would translate into improved estimates of human risk is questionable. Thus, it does not appear possible at present to develop a quantitative approach that would be generally applicable and that would offer significant improvements upon the crude bounding estimates of the type provided by the LMS model. Draft USEPA guidelines for cancer risk assessment incorporate an approach similar to the LMS for carcinogens having a linear mode of action. However, under these guidelines quantitative estimates of low-dose risks would not be developed for carcinogens having a non-linear mode of action; instead dose-response modelling would be used in the experimental range to calculate an LED10* (a statistical lower bound on the dose corresponding to a 10% increase in risk), and safety factors would be applied to the LED10* to determine acceptable exposure levels for humans. This approach is very similar to the one presently used by USEPA for non-carcinogens. Rather than using one approach for carcinogens believed to have a linear mode of action and a different approach for all other health effects, it is suggested herein that it would be more appropriate to use an approach conceptually similar to the 'LED10*-safety factor' approach for all health effects, and not to routinely develop quantitative risk estimates from animal data.

Animals↗
PubMedDate not supplied

Gas chromatographic/electron capture detection method for determination of chlorinated acids in water: collaborative study.

A U.S. Environmental Protection Agency (USEPA) interlaboratory method validation study was conducted on USEPA Method 515.1, "Determination of Chlorinated Acids in Water by Gas Chromatography with an Electron Capture Detector." This method is one of the 6 pesticide methods developed for the USEPA National Pesticide Survey (NPS). Method recovery and precision for analyses of sub-ppb to low-ppb concentrations of chlorinated acids were determined in reagent water and finished drinking waters. The analytes evaluated in the study included the 12 pesticides that were quantitatively measured in the National Pesticide Survey (bentazon, 2,4-D, 2,4-DB, 3,5-dichlorobenzoic acid, DCPA-diacid, dicamba, dichlorprop. 5-hydroxydicamba, pentachlorophenol, picloram, 2,4,5-T, and 2,4,5-TP) and 5 pesticides (acifluorfen, chloramben, dalapon, dinoseb, and 4-nitrophenol) that were only qualitatively assessed in the National Pesticide Survey because of recognized method imprecision. The study design was based on Youden's nonreplicate plan for collaborative tests of analytical methods. The waters were spiked with 17 chlorinated acids, each at 6 concentration levels, prepared as 3 Youden pairs. Eight laboratories extracted the spiked test waters at pH < 2 with ethyl ether, performed a solvent exchange with methyl tert-butyl ether, prepared methyl esters of the extracted acids using diazomethane, and analyzed an aliquot of each derivatized extract by gas chromatography with electron capture detection. The submitted data were analyzed using a USEPA computer program, which measured recovery and precision for each of the 17 compounds and compared the performance of the method between water types. Method 515.1 was judged acceptable for the 12 NPS analytes recovered quantitatively; mean percent recoveries at 10-15 times the method detection limits ranged from 79 to 105% in reagent water and from 75 to 123% in finished drinking water. In reagent water, overall precision (reproducibility relative standard deviation, RSDR) ranged from 9.6 to 34.2% and in finished drinking water, the RSDR ranged from 11.9 to 37.0%. Single-analyst precision (RSD for repeatability, RSDr) ranged from 5.8 to 17.7% in reagent water and from 4.6 to 27.9% in drinking water. Results for the 5 other NPS analytes were too inaccurate or imprecise and, for these compounds, supported use of the method for qualitative measurements only; the 5 compounds are not included in the adopted method. The method has been adopted first action by AOAC INTERNATIONAL for determination of residues of 12 chlorinated acids in finished drinking water.

Analysis of Variance↗
PubMed2007

Survey of dioxin-like compounds in dairy feeds in the United States.

The United States Environmental Protection Agency (USEPA) has completed a survey of dioxin-like compounds (including 17 dioxin and furan (CDD/F) congeners and 12 coplanar polychlorinated biphenyl (PCBs) congeners) in dairy feeds from 10 dairy research facilities around the United States, sampling the overall mixtures and the major and minor feed components. Low levels of dioxin were found in all feed mixtures with an average concentration of 0.05 pg/g (ppt) toxic equivalent (TEQ) dry weight. This is lower than previously found in dairy feeds by about a factor of 4. While it is possible that generally lower levels of dioxins in the environment in recent years may explain this result, examinations of the data suggest that the oven drying used to prepare the wet feed samples could have resulted in a loss of dioxins from the feed materials. The percentage of the total TEQ due to CDD/Fs was about four times that of PCBs. Leafy vegetations in the feed (the silages and the hays) had concentrations about twice as high as nonleafy, protected vegetation of the feeds (the ground or meal corn, cottonseed, and others). Minor components did not significantly influence the final feed mixture concentration of dioxin TEQ. However, in one of the feed mixtures, a minor component with a high concentration of 38.5 ppt TEQ effectively doubled the concentration of the overall feed mixture.

Animal Feed↗
PubMed2004

Worker exposure standard for phosphine gas.

The 1998 U.S. Environmental Protection Agency Office of Pesticide Programs (OPP) re-registration eligibility decision (RED) for phosphine fumigants has generated much interest in defining safe levels of exposure for workers and worker bystanders. This report summarizes the pertinent literature on phosphine toxicity, including animal inhalation studies and human epidemiology studies, and also describes a margin-of-exposure (MOE) analysis based on available worker exposure data. In addition, a safe occupational exposure limit is estimated using typical OPP assumptions, after determination of appropriate uncertainty factors, based on quality of data in the principal study and pharmacokinetic considerations. While a conservative 8-hour time-weighted average (TWA) of 0.1 ppm was calculated, the overall weight of evidence, from a risk-management perspective, supports a conclusion that an occupational TWA of 0.3 ppm provides adequate health protection. In addition, a 15-minute short-term exposure limit (STEL) of 3 ppm was estimated. Finally, in contrast to the MOE analysis described in the OPP's phosphine RED, the MOE analysis described herein does not indicate that fumigation workers are currently being exposed to unacceptable levels of phosphine. Collectively, these findings support the occupational exposure limits of 0.3 ppm (8-hour TWA) and 1 ppm (STEL) established in the updated applicator's manuals for phosphine-generating products, which recently received approval from OPP.

Administration, Inhalation↗
PubMed2002

Assessing homeland chemical hazards outside the military gates: industrial hazard threat assessments for department of defense installations.

As part of comprehensive joint medical surveillance measures outlined by the Department of Defense, the US Army Center for Health Promotion and Preventive Medicine (USACHPPM) is beginning to assess environmental health threats to continental US military installations. A common theme in comprehensive joint medical surveillance, in support of Force Health Protection, is the identification and assessment of potential environmental health hazards, and the evaluation and documentation of actual exposures in both a continental US and outside a continental US setting. For the continental US assessments, the USACHPPM has utilized the US Environmental Protection Agency (EPA) database for risk management plans in accordance with Public Law 106-40, and the toxic release inventory database, in a state-of the art geographic information systems based program, termed the Consequence Assessment and Management Tool Set, or CATS, for assessing homeland industrial chemical hazards outside the military gates. As an example, the US EPA toxic release inventory and risk management plans databases are queried to determine the types and locations of industries surrounding a continental US military installation. Contaminants of concern are then ranked with respect to known toxicological and physical hazards, where they are then subject to applicable downwind hazard simulations using applicable meteorological and climatological data sets. The composite downwind hazard areas are mapped in relation to emergency response planning guidelines (ERPG), which were developed by the American Industrial Hygiene Association to assist emergency response personnel planning for catastrophic chemical releases. In addition, other geographic referenced data such as transportation routes, satellite imagery and population data are included in the operational, equipment, and morale risk assessment and management process. These techniques have been developed to assist military medical planners and operations personnel in determining the industrial hazards, vulnerability assessments and health risk assessments to continental United States military installations. These techniques and procedures support the Department of Defense Force Protection measures, which provides awareness of a terrorism threat, appropriate measures to prevent terrorist attacks and mitigate terrorism's effects in the event that preventive measures are ineffective.

Data Collection↗
PubMed2005

Fine particulate matter national ambient air quality standards: public health impact on populations in the northeastern United States.

In this article we identify the magnitude of general and susceptible populations within the northeastern United States that would benefit from compliance with alternative U.S. Environmental Protection Agency (EPA) annual and 24-hr mass-based standards for particulate matter (PM) with an aerodynamic diameter < or = 2.5 microm (PM2.5). Understanding the scale of susceptibility in relation to the stringency or protectiveness of PM standards is important to achieving the public health protection required by the Clean Air Act of 1970. Evaluative tools are therefore necessary to place into regulatory context available health and monitoring data appropriate to the current review of the PM National Ambient Air Quality Standards (NAAQS). Within the New England, New Jersey, and New York study area, 38% of the total population are < 18 or > or =65 years of age, 4-18% of adults have cardiopulmonary or diabetes health conditions, 12-15% of children have respiratory allergies or lifetime asthma, and 72% of all persons (across child, adult, and elderly age groups) live in densely populated urban areas with elevated PM2.5 concentrations likely creating heightened exposure scenarios. The analysis combined a number of data sets to show that compliance with a range of alternative annual and 24-hr PM2.5 standard groupings would affect a large fraction of the total population in the Northeast. This work finds that current PM2.5 standards in the eight-state study area affect only 16% of the general population, who live in counties that do not meet the existing annual/24-hr standard of 15/65 microg/m3. More protective PM2.5 standards recommended or enacted by California and Canada would protect 84-100% of the Northeast population. Standards falling within current ranges recommended by the U.S. EPA would protect 29-100% of the Northeast population. These considerations suggest that the size of general and susceptible populations affected by the stringency of alternative PM standards has broad implications for risk management and direct bearing on the U.S. EPA's current NAAQS review and implementation.

Adolescent↗
PubMed2005

The screening of chemicals for juvenoid-related endocrine activity using the water flea Daphnia magna.

U.S. Environmental Protection Agency is charged with developing a screening and testing paradigm for detecting endocrine toxicity of chemicals that are subject to regulation under the Food Quality Protection and the Safe Drinking Water Acts. In this study, we developed and evaluated a screening assay that could be employed to detect juvenoid-related endocrine-modulating activity in an invertebrate species. Juvenoid activity, anti-juvenoid activity, and juvenoid potentiator activity of chemicals was assessed using the water flea Daphnia magna. Male sex determination is under the regulatory control of juvenoid hormone, presumably methyl farnesoate, and this endpoint was used to detect juvenoid modulating activity of chemicals. Eighteen chemicals were evaluated for juvenoid agonist activity. Positive responses were detected with the juvenoid hormones methyl farnesoate and juvenile hormone III along with the insect growth regulating insecticides pyriproxyfen, fenoxycarb, and methoprene. Weak juvenoid activity also was detected with the cyclodiene insecticide dieldrin. Assays performed repetitively with compounds that gave either strong positive, weak positive, or negative response were 100% consistent indicating that the assay is not prone to false positive or negative responses. Five candidate chemicals were evaluated for anti-juvenoid activity and none registered positive. Four chemicals (all trans-retinoic acid, methoprene, kinoprene, bisphenol A) also were evaluated for their ability to potentiate the activity of methyl farnesoate. All registered positive. Results demonstrate that an in vivo assay with a crustacean species customarily employed in toxicity testing can be used to effectively screen chemicals for juvenoid-modulating activity.

Animals↗
PubMed2003

Water quality guidance for protection of freshwater mussels (Unionidae) from ammonia exposure.

Ammonia toxicity data for freshwater mussels (Unionidae), a significantly imperiled taxa, were used to derive estimates of concentrations that would not likely be harmful in acute and chronic exposures and to assess the protectiveness of current U.S. Environmental Protection Agency (U.S. EPA) water quality criteria to this family of organisms. Thirty acute (24-96-h) median lethal concentrations (LC50s), covering 10 species in eight unionid genera, were used to calculate genus mean acute values (GMAVs) ranging from 2.56 to 8.97 mg/L total ammonia as N at pH 8. Freshwater mussels are at the sensitive end of the range when added to the GMAVs from the database used to derive the U.S. EPA criteria maximum concentration (CMC). We derived two estimates of acute exposure water quality guidance for the protection of freshwater mussels (CMC(FM)) by a recalculation of the CMC after adding freshwater mussel GMAVs to the U.S. EPA data set. The CMC(FM)s of 1.75 and 2.50 mg/L total ammonia as N at pH 8 average 60% less than the U.S. EPA CMC of 5.62 mg/L total ammonia as N at pH 8 for application when salmonids are present. These values average about 75% less than the CMC for application when salmonids are absent. No chronic ammonia exposure data existed for unionids. Thus, we applied a range of estimated acute:chronic ratios to the acute toxicity data set, expanded with the freshwater mussel GMAVs. to estimate continuous ammonia concentrations that may be protective of freshwater mussels. These estimates ranged from 0.3 to 1.0 mg/L total ammonia as N at pH 8, about 20 to 75% less than the U.S. EPA criteria continuous concentration (CCC) of 1.24 mg/L total ammonia as N at pH 8 and 25 degrees C. The current numeric criteria for ammonia may not be protective of mussels, more than half of whose nearly 300 species are in decline in North America. While the CMC(FM) and CCC(FM) are not equivalent to revised U.S. EPA criteria, they are offered as interim guidance for the protection of freshwater mussels.

Ammonia↗
PubMed2001

Identifying sources of stress to native aquatic fauna using a watershed ecological risk assessment framework.

The free-flowing Clinch and Powell River Basin, located in southwestern Virginia, United States, historically had one of the richest assemblages of native fish and freshwater mussels in the world. Nearly half of the species once residing here are now extinct, threatened, or endangered. The United States Environmental Protection Agency's framework for conducting an ecological risk assessment was used to structure a watershed-scale analysis of human land use, in-stream habitat quality, and their relationship to native fish and mussel populations in order to develop future management strategies and prioritize areas in need of enhanced protection. Our analyses indicate that agricultural and urban land uses as well as proximity to mining activities and transportation corridors are inversely related to fish index of biotic integrity (IBI) and mussel species diversity. Forward stepwise multiple regression analyses indicated that coal mining had the most impact on fish IBI followed by percent cropland and urban area in the riparian corridor (R2 = 0.55, p = 0.02); however, these analyses suggest that other site-specific factors are important. Habitat quality measures accounted for as much as approximately half of the variability in fish IBI values if the analysis was limited to sites within a relatively narrow elevation range. These results, in addition to other data collected in this watershed, suggest that nonhabitat-related stressors (e.g., accidental chemical spills) also have significant effects on biota in this basin. The number of co-occurring human land uses was inversely related to fish IBI (r = -0.49, p < 0.01). Sites with > or = 2 co-occurring land uses had >90% probability of having <2 mussel species present. Our findings predict that many mussel concentration sites are vulnerable to future extirpation. In addition, our results suggest that protection and enhancement of naturally vegetated riparian corridors, better controls of mine effluents and urban runoff, and increased safeguards against accidental chemical spills, as well as reintroduction or augmentation of threatened and endangered species, may help sustain native fish and mussel populations in this watershed.

Agriculture↗
PubMed1999

A cancer risk assessment of di(2-ethylhexyl)phthalate: application of the new U.S. EPA Risk Assessment Guidelines.

The current United States Environmental Protection Agency (EPA) classification of di(2-ethylhexyl)phthalate (DEHP) as a B2 "probable human" carcinogen is based on outdated information. New toxicology data and a considerable amount of new mechanistic evidence were used to reconsider the cancer classification of DEHP under EPA's proposed new cancer risk assessment guidelines. The total weight-of-evidence clearly indicates that DEHP is not genotoxic. In vivo administration of DEHP to rats and mice results in peroxisome proliferation in the liver, and there is strong evidence and scientific consensus that, in rodents, peroxisome proliferation is directly associated with the onset of liver cancer. Peroxisome proliferation is a transcription-mediated process that involves activation by the peroxisome proliferator of a nuclear receptor in rodent liver called the peroxisome proliferator-activated receptor (PPARalpha). The critical role of PPARalpha in peroxisomal proliferation and carcinogenicity in mice is clearly established by the lack of either response in mice genetically modified to remove the PPARalpha. Several mechanisms have been proposed to explain how, in rodents, peroxisome proliferation can lead to the formation of hepatocellular tumors. The general consensus of scientific opinion is that PPARalpha-induced mitogenesis and cell proliferation are probably the major mechanisms responsible for peroxisome proliferator-induced hepatocarcinogenesis in rodents. Oxidative stress appears to play a significant role in this increased cell proliferation. It triggers the release of TNFalpha by Kupffer cells, which in turn acts as a potent mitogen in hepatocytes. Rats and mice are uniquely responsive to the morphological, biochemical, and chronic carcinogenic effects of peroxisome proliferators, while guinea pigs, dogs, nonhuman primates, and humans are essentially nonresponsive or refractory; Syrian hamsters exhibit intermediate responsiveness. These differences are explained, in part, by marked interspecies variations in the expression of PPARalpha, with levels of expression in humans being only 1-10% of the levels found in rat and mouse liver. Recent studies of DEHP clearly indicate a nonlinear dose-response curve that strongly suggests the existence of a dose threshold below which tumors in rodents are not induced. Thus, the hepatocarcinogenic effects of DEHP in rodents result directly from the receptor-mediated, threshold-based mechanism of peroxisome proliferation, a well-understood process associated uniquely with rodents. Since humans are quite refractory to peroxisomal proliferation, even following exposure to potent proliferators such as hypolipidemic drugs, it is concluded that the hepatocarcinogenic response of rodents to DEHP is not relevant to human cancer risk at any anticipated exposure level. DEHP should be classified an unlikely human carcinogen with a margin of exposure (MOE) approach to risk assessment. The most appropriate and conservative point of reference for assessing MOEs should be 20 mg/kg/day, which is the mouse NOEL for peroxisome proliferation and increased liver weight. Exposure of the general human population to DEHP is approximately 30 microg/kg body wt/day, the major source being from residues in food. Higher exposures occur occupationally [up to about 700 microg/kg body wt/day (mainly by inhalation) based on current workplace standards] and through use of certain medical devices [e.g., up to 457 microg/kg body wt/day for hemodialysis patients (intravenous)], although these have little relevance because the routes of exposure bypass critical activation enzymes in the gastrointestinal tract.

Animals↗
PubMed1999

Performance assessments of nuclear waste repositories: a dialogue on their value and limitations.

Performance Assessment (PA) is the use of mathematical models to simulate the long-term behavior of engineered and geologic barriers in a nuclear waste repository; methods of uncertainty analysis are used to assess effects of parametric and conceptual uncertainties associated with the model system upon the uncertainty in outcomes of the simulation. PA is required by the U.S. Environmental Protection Agency as part of its certification process for geologic repositories for nuclear waste. This paper is a dialogue to explore the value and limitations of PA. Two "skeptics" acknowledge the utility of PA in organizing the scientific investigations that are necessary for confident siting and licensing of a repository; however, they maintain that the PA process, at least as it is currently implemented, is an essentially unscientific process with shortcomings that may provide results of limited use in evaluating actual effects on public health and safety. Conceptual uncertainties in a PA analysis can be so great that results can be confidently applied only over short time ranges, the antithesis of the purpose behind long-term, geologic disposal. Two "proponents" of PA agree that performance assessment is unscientific, but only in the sense that PA is an engineering analysis that uses existing scientific knowledge to support public policy decisions, rather than an investigation intended to increase fundamental knowledge of nature; PA has different goals and constraints than a typical scientific study. The "proponents" describe an ideal, six-step process for conducting generalized PA, here called probabilistic systems analysis (PSA); they note that virtually all scientific content of a PA is introduced during the model-building steps of a PSA; they contend that a PA based on simple but scientifically acceptable mathematical models can provide useful and objective input to regulatory decision makers. The value of the results of any PA must lie between these two views and will depend on the level of knowledge of the site, the degree to which models capture actual physical and chemical processes, the time over which extrapolations are made, and the proper evaluation of health risks attending implementation of the repository. The challenge is in evaluating whether the quality of the PA matches the needs of decision makers charged with protecting the health and safety of the public.

Geological Phenomena↗
PubMed1996

Surveillance for waterborne-disease outbreaks--United States, 1993-1994.

PROBLEM/CONDITION: Since 1971, CDC and the U.S. Environmental Protection Agency have maintained a collaborative surveillance system for collecting and periodically reporting data that relate to occurrences and causes of waterborne-disease outbreaks (WBDOs). REPORTING PERIOD COVERED: This summary includes data for January 1993 through December 1994 and for previously unreported outbreaks in 1992. DESCRIPTION OF THE SYSTEM: The surveillance system includes data about outbreaks associated with water intended for drinking (i.e., drinking water) and those associated with recreational water. State, territorial, and local public health departments are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC on a standard form. RESULTS: For the 2-year period 1993-1994, 17 states and one territory reported a total of 30 outbreaks associated with drinking water. These outbreaks caused an estimated 405,366 persons to become ill, including 403,000 from an outbreak of cryptosporidiosis in Milwaukee, the largest WBDO ever documented in the United States, and 2,366 from the other 29 outbreaks. No etiologic agent was identified for five (16.7%) of the 30 outbreaks. The protozoan parasites Giardia lamblia and Cryptosporidium parvum caused 10 (40.0%) of the 25 outbreaks for which the etiologic agent was identified. Two outbreaks of cryptosporidiosis occurred in large metropolitan areas (i.e., Milwaukee and Las Vegas/Clark County) and were associated with deaths among immunocompromised persons. The waterborne nature of these two outbreaks was not recognized until at least 2 weeks after the onset of the Milwaukee outbreak and until after the end of the Las Vegas outbreak. Campylobacter jejuni was implicated for three outbreaks and the following pathogens for one outbreak each: Shigella sonnei, Shigella flexneri, non-O1 Vibrio cholerae (in a U.S. territory; the vehicle was commercially bottled water), and Salmonella serotype Typhimurium (the outbreak was associated with seven deaths). Eight outbreaks of chemical poisoning were reported: three were caused by lead (one case each), two by fluoride, two by nitrate and one by copper. Twenty (66.7%) of the 30 outbreaks were associated with a well-water source. Fourteen states reported a total of 26 outbreaks associated with recreational water, in which an estimated 1,714 persons became ill. Fourteen (53.8%) of these 26 were outbreaks of gastroenteritis. The etiologic agent in each of these 14 outbreaks was identified; 10 (71.4%) were caused by G. lamblia or C. parvum. Six of these 10 were associated with chlorinated, filtered pool water, and three with lake water. One of the latter was the first reported outbreak of cryptosporidiosis associated with the recreational use of lake water. Four outbreaks of lake water-associated bacterial gastroenteritis were reported, two caused by S. sonnei, one by S. flexneri, and one by Escherichia coli O157:H7. Nine outbreaks of hot tub- whirlpool-, or swimming pool-associated pseudomonas dermatitis were reported. Two outbreaks of swimming pool-associated dermatitis had a suspected chemical etiology. The child who had the one reported case of primary amebic meningoencephalitis, caused by infection with Naegleria fowleri, died. INTERPRETATION: The number of WBDOs reported annually has been similar for each year during 1987-1994, except for an increase in 1992. Protozoan parasites, especially C. parvum and G. lamblia, remain important etiologic agents of WBDOs. The outbreaks of cryptosporidiosis in Milwaukee and Las Vegas demonstrate that WBDOs can occur in large metropolitan areas. Surveillance methods are needed that expedite the detection of WBDOs and the institution of preventive measures (e.g., boil-water advisories). ACTIONS TAKEN: Surveillance data that identify the types of water systems, their deficiencies, and the etiologic agents associated with outbreaks are used to evaluate the adequacy of current technologies for prov

Animals↗
PubMed2006

Analysis of primary fine particle national ambient air quality standard metrics.

In accordance with the Clean Air Act, the U.S. Environmental Protection Agency (EPA) is currently reviewing its National Ambient Air Quality Standards for particulate matter, which are required to provide an adequate margin of safety to populations, including susceptible subgroups. Based on the latest scientific, health, and technical information about particle pollution, EPA staff recommends establishing more protective health-based fine particle standards. Since the last standards review, epidemiologic studies have continued to find associations between short-term and long-term exposure to particulate matter and cardiopulmonary morbidity and mortality at current pollution levels. This study analyzed the spatial and temporal variability of fine particulate (PM2.5) monitoring data for the Northeast and the continental United States to assess the protectiveness of various levels, forms, and combinations of 24-hr and annual health-based standards currently recommended by EPA staff and the Clean Air Scientific Advisory Committee. Recommended standards have the potential for modest or substantial increases in protection in the Northeast, ranging from an additional 13-83% of the population of the region who are living in areas not likely to meet new standards and thereby benefiting from compliance with more protective air pollution controls. Within recommended standard ranges, an optimal 24-hr (98th percentile)/annual standard suite occurs at 30/12 microg/m3, providing short- and long-term health protection for a substantial percentage of both Northeast (84%) and U.S. (78%) populations. In addition, the Northeast region will not benefit as widely as the nation as a whole if less stringent standards are selected. Should the 24-hr (98th percentile) standard be set at 35 microg/m3, Northeast and U.S. populations will receive 16-48% and 7-17% less protection than a 30 microg/m3 standard, respectively, depending on the level of the annual standard. A 30/12 microg/m3 standard suite also provides nearly equivalent 24-hr and annual control of PM2.5 distributions across the United States, thereby ensuring a more uniform and consistent level of protection than unmatched or "controlling" and "backstop" standards. This could occur even within EPA staff's recommended range of standard suites, where 22-43% of the monitors in the country could meet a controlling standard but fail to meet the combined backstop standard, resulting in inconsistent short- and long-term protection across the country. An equivalent standards combination of 30/12 microg/m3 would minimize the wide variation of protectiveness of 24-hr and annual PM2.5 concentrations. Furthermore, given recent associations of subdaily exposures and acute adverse health effects, in the absence of a subdaily averaging metric, a stringent 24-hr standard will more effectively control maximum hourly and multihourly peak concentrations than a weaker standard.

Air Pollutants↗
PubMed2003

Uncertainties for endocrine disrupters: our view on progress.

The hypothesis that hormonally active compounds in the environment--endocrine disrupters--are having a significant impact on human and ecological health has captured the public's attention like no other toxicity concern since the publication of Rachel Carson's Silent Spring 1962. In the early 1990s, Theo Colborn and others began to synthesize information about the potential impacts of endocrine-mediated toxicity in the scientific literature (Colborn and Clement, 1992) and the popular press (Colborn et al., 1997). Recognizing the possibility of an emerging health threat, the U.S. Environmental Protection Agency (EPA) convened two international workshops in 1995 (Ankley et al., 1997; Kavlock et al., 1996) that identified research needs relative to future risk assessments for endocrine-disrupting chemicals (EDCs). These workshops identified effects on reproductive, neurological, and immunological function, as well as carcinogenesis as the major endpoints of concern and made a number of recommendations for research. Subsequently, the EPA developed a research strategy to begin addressing the recommendations (EPA, 1998a), and the federal government as a whole, working through the White House's Committee on the Environment and Natural Resources, increased funding levels and coordinated research programs to fill the major data gaps (Reiter et al., 1998). In parallel with these research efforts that were attempting to define the scope and nature of the endocrine disruptor hypothesis, the U.S. Congress added provisions to the Food Quality Protection Act (FQPA) and the Safe Drinking Water Act of 1996 to require the testing of food-use pesticides and drinking water contaminants, respectively, for estrogenicity and other hormonal activity. These bills were enacted into law, giving the EPA the mandate to implement them. The EPA, with the help of an external advisory committee, the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), determined that other hormonal activity should include androgens and compounds that affect thyroid function, and expanded the mandate to include all chemicals under EPA's jurisdiction, potentially including the 70,000 chemicals regulated under the Toxic Substances Control Act (Endocrine Disruptor Screening and Testing Advisory Committee [EDSTAC], 1998). EDSTAC recommended an extensive process of prioritization, screening, and testing of chemicals for endocrine-disrupting activity, including a screening battery that involves a combination of at least eight in vitro and in vivo assays spanning a number of taxa (EDSTAC, 1998). What started out as a hypothesis has become one of the biggest testing programs conceived in the history of toxicology and the only one that has ever been based on mechanism of action as its premise. As we pass the 10th anniversary of the emergence of the endocrine disruptor hypothesis, it is useful to look back on the progress that has been made in answering the nine questions posed as data gaps in the EPA's research strategy (EPA, 1998a)--not only to see what we have learned, but also to examine whether the questions are still appropriate for the goal, what gaps remain, and what directions should be emphasized in the future.

Animals↗
PubMed1997

FIFRA Subdivision F testing Guidelines: are these tests adequate to detect potential hormonal activity for crop protection chemicals? Federal Insecticide, Fungicide, and Rodenticide Act.

Recently, a major topic of discussion has been the impact of synthetic chemicals that possess the capacity to alter hormonal activity, the so-called "endocrine modulators," with potentially the capacity to alter the reproductive capability of humans. Particularly, various synthetic pesticides and industrial chemicals that persist in the environment and/or bioaccumulate have been implicated. Further, it has been alleged that the standard tests for pesticide registration as required by the U.S. Environmental Protection Agency (EPA) and other regulatory agencies may be inadequate to detect endocrine modulating effects. To address these shortcomings, it has been proposed that very specific tests for estrogen receptor binding, or in vitro cell response to chemicals, be used to identify potential endocrine modulators. However, such approaches have certain flaws that limit their application as screens. First, very specific tests, like receptor binding, evaluate only a single chemical event per test. Such tests do not measure toxicity or biological response. Isolated systems are very important for studying mechanisms of action or structure activity relationships, but can only provide a preliminary screen for a single mechanism of toxicity. Isolated systems can not be used to regulate a chemical without additional information. Second, they fail to test many other parts of the neuroendocrine control of the reproductive system. Testing for adverse effects in highly specific in vitro systems failed to replace whole-animal models in carcinogenesis and will also fail in reproductive toxicology because this system is too complicated for such as in vitro approach to be accurately predictive. Advanced tests, such as the EPA multigeneration study, are more effective, and reliable means for evaluation than any specific and narrowly focused screening tests. Experience has shown that a better approach to testing chemicals is to evaluate their effects on the whole animal. When one part of the system is adversely affected, various processes may be indirectly affected and can be detected in the animal model. For example, a modulation of testosterone synthesis could lead to (1) altered accessory sex organ morphology, size, and function; (2) decreased sperm counts; and (3) even decreased fertility. These and many other effects would be noted in toxicity studies that are already required for the registration of crop protection chemicals. The developmental and reproductive toxicity guidelines were recently reviewed in a hearing that included the representatives from the EPA, the public, and the Scientific Advisory Panel. The EPA kept the basic study design the same, but added a few new endpoints to further assess chemical-induced effects on reproductive development and function. The review presented herein concentrates on the required Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) testing for pesticides, and demonstrates how the massive arrays of sensitive endocrine endpoints that are delineated in FIFRA Subdivision F have been successfully used to detect both weak and potent hormonally modulating chemicals. For example, (1) diethyl-stilbestrol (DES), which is a potent synthetic therapeutic estrogen, (2) DDT, which is weakly estrogenic but persistent and bioaccumulating, and (3) dioxins, which have antiestrogenic properties, were all found as being hormonally active in tests similar or identical to FIFRA tests. All food-use pesticides have been evaluated using a comprehensive multigeneration reproduction test. Hence, the FIFRA testing procedures have been demonstrated to identify endocrine modulators of sufficient potency to represent a concern to human health.

Animals↗