Amplified spontaneous emission of surface plasmon polaritons and limitations on the increase of their propagation length.

Amplified spontaneous emission of surface plasmon polaritons (SPPs) at the interface of a resonant gain medium has been observed. The amplification is accompanied by significant spectral narrowing and limits the gain available for compensation of SPP propagation losses. The effect is similar to the deteriorating influence of amplified spontaneous emission in laser resonators.

An intervention analysis for the reduction of exposure to methylmercury from the consumption of seafood by women of child-bearing age.

A previously developed exposure model was used [Risk Anal. 22 (2002) 689] to assess the effectiveness of various advisory scenarios on minimizing mercury (Hg) blood levels via the consumption of commercial seafood, both finfish and shellfish. This exposure model was developed to predict levels of Hg in blood in women of child-bearing age in the US based on the frequency of seafood consumption, the amount of seafood consumed per serving, and the types of seafood consumed. Steady-state relationships that employed descriptive statistics to account for toxicokinetic variation were used to predict levels of Hg in blood. The model incorporates an uncertainty dimension that is intended to represent the range of plausible interpretations of the data. The predictability of the model was confirmed via the use of National Health and Nutrition Examination Survey (NHANES) blood Hg data. In the present analysis, the model was used to predict the impact of limitations in the amount or types of seafood consumed on blood Hg levels. Specifically, simulations for various advisory scenarios were developed on the basis of limitations on total consumption of seafood, elimination of the consumption of certain species altogether, and/or a combination of both. In the baseline model, the median (uncertainty) estimates for the 50th, 95th, and 99th per capita population percentiles were 1.25, 8.2, and 16.1 ppb blood Hg, respectively. After restriction of seafood consumption to no more than 12 oz/week, the median (uncertainty) estimates for the 50th, 95th, and 99th per capita population percentiles were 1.22, 6.8, and 10.6 ppb blood Hg, respectively. Elimination of MeHg species, with average concentrations above 0.6 ppm, resulted in very modest decrements in Hg blood levels, in comparison to either the baseline or the reduced consumption scenarios. These results suggest that strategies to reduce MeHg exposure by reducing the amount of fish consumed (e.g., 12 oz/week) are more effective at eliminating the high end of the exposure distribution than are strategies intended to change the types of fish consumed.

Persistent organic pollutants exposure assessment using the US Total Diet Study.

The assessment presented in the core paper of this debate by Schafer and Kegley does not adequately describe the computational methodology or sources of data that were used to estimate exposures. While it is difficult to determine from the article, the exposure estimates seem to be very dependent on action levels, rather than on empirically derived data. There is no adequate presentation of analytical methods, limits of detection, or the significance of non-detects in deriving estimates of exposure.

US Food and Drug Administration's Total Diet Study: intake of nutritional and toxic elements, 1991-96.

The Food and Drug Administration (FDA) has conducted the Total Diet Stuty (TDS) annually since 1961. The TDS is designed to monitor the US food supply for levels of toxic chemical contaminants (pesticide residues, industrial chemicals and toxic elements) and nutritional elements. Foods are generally collected four times a year, once from each of four regions of the country. The foods are prepared table-ready before being analysed. From the results of the TDS, dietary, intakes of these analytes are estimated for selected age-sex groups in the US population. This paper reports on the dietary intake of 10 nutritional and four toxic elements based on measurements made in foods collected in the TDS between 1991 and late 1996. Average daily intakes were estimated for 14 age-sex groups in the US population, as well as the contribution of specific food groups to total intakes. For most nutritional elements, teenage boys and adult males had the highest daily intakes. Intakes by infants were below the intake references for seven of 10 nutritional elements, and young girls and women had inadequate intakes of at least half the nutritional elements. Intakes by children between 2 and 10 years of age, teenage boys, and adult males met or exceeded the reference intakes for the majority of nutritional elements. Intakes by all population groups were well below the reference intakes for all toxic elements.

Exposure assessment of dioxins/furans consumed in dairy foods and fish.

Dioxins/furans are ubiquitous environmental contaminants whose primary route of human exposure occurs via the consumption of fatty foods of animal origin. The US FDA conducted a market basket survey of dairy products and commercial fish and shellfish to obtain data on levels of 17 dioxin/furan congeners (2, 3, 7, 8-congeners) in the US. The dairy products sampled included various cheeses (American, cheddar, Swiss, cottage), ice cream, yogurt, butter, and milk. The finfish and shellfish (molluscs and crustacea) sampled are those marine species consumed in the greatest amounts and include canned tuna, shrimp, cod, blue crab, and oysters. Catfish was sampled because it is the dominant aquaculture species. Samples were collected in 1995/96 and analysis for 17 dioxin/furan congeners was performed by high-resolution gas chromatography following extraction and clean-up. Limits of detection (LOD) and quantitation (LOQ) for each congener in each food were reported. Point estimates of exposure were calculated using a 3-day (1-day diary plus 2-day recall) food consumption survey for eaters-only and for the general population (USDA/CSFII, 1989-92). Toxicity equivalency factors (TEFs) developed by the World Health Organization (1997) were used to derive overall dioxin/furan toxicity equivalents (TEQ) for each sample food. Mean estimates of TEQ exposure for each food were derived using five values for non-detects (ND = 0; ND = 1/2 LOD or LOQ, ND = LOD or LOQ) on both a total sample and eaters-only basis. Using zero and the LOD provide lower and upper bounds on the range of estimated exposure, respectively. The bounds on mean dioxin intakes (pg/person/day) calculated for consumers of specific foods were estimated as follows (using zero or LOD for non-detects): butter (0.5-11), cheese (1.6-3.2), ice cream (4-19), yogurt (0.8-28), catfish (148-150), fish (other than catfish) (0.03-9), crustacea (32-35), mollusks (16.1-16.6), and shrimp (0.09-4.5). Exposure estimates derived by the five ND-methods are strongly dependent on the LOD and LOQ and represent upper bound estimates of exposure. Uncertainty in the exposure estimates is reduced with refinements in the analytical method.

Methods for projecting long-term dietary exposure from short-term survey data for environmental contaminants.

Public health risk assessments often involve dietary exposures over long periods of time. However, most information about dietary consumption habits comes from short-term surveys that are conducted for periods of three days or less. When employed for characterizing long-term exposures, short-term surveys are likely to underestimate the number of persons consuming a particular food, while overestimating the amount consumed by each individual. Direct application of short-term data is particularly misleading for foods that are consumed infrequently. If a more accurate population estimate for chronic dietary intake is needed for a risk assessment, then two general techniques may be considered. The first method is simpler, while the second is more accurate. Both methods require information about the size of the population consuming the food over the long-term period. The simpler fractional adjustment method reduces consumption across the entire distribution by the ratio of consumer population sizes. Since this method will tend to underestimate high-end exposures and overestimate low-end exposures, it is most useful as a quick bounding exercise. Since short-term surveys are better at characterizing the behavior of frequent consumers, a second method employs an exponential function to reduce the low end of the population distribution by a greater amount than the high end. If available, additional information may be used to select the parameter values for the exponential adjustment. Otherwise, an uncertainty range may be used for the parameter values. Since the frequency-based method is more complex, it is most valuable when used as part of a chronic exposure simulation. Examples of both methods are given for the estimation of chronic wine consumption.

Dietary arsenic intakes in the United States: FDA Total Diet Study, September 1991-December 1996.

The FDA has conducted the Total Dietary Study (TDS), a yearly market basket programme, since 1961. It is designed to monitor the levels of toxic chemical contaminants (pesticide residues, industrial and elemental contaminants) and essential nutrients in the US food supply. It also provides information on trends in dietary concentrations and exposures for the general population. Foods are collected from retail stores once a year from each of four geographic areas of the US and are analysed either after preparation/cooking or as ready-to-eat. The latest TDS (1991-1997) data show that arsenic (inorganic and organic, > or = 0.03 ppm) was found in 63 (24%) of the 261-264 foods/mixed dishes analysed. The highest concentration was found in seafood, followed by rice/rice cereal, mushrooms, and poultry. Based on the United States Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey, the estimated daily total arsenic average intakes, in microgram/day, are: 2 for infants, 23 for toddlers, 20 for 6-year-old children, 13 for 10-year-old children, 15 for 14-16-year-old boys, 21 for 14-16-year-old girls, 57 for 25-30-year-old men, 28 for 25-30-year-old women, 47 for 40-45-year-old men, 37 for 40-45-year-old women, 92 for 60-65-year-old men, 72 for 60-65-year-old women, 69 for 70-year-old men, and 42 for 70-year-old women. Of the estimated total arsenic intakes for infants, 42% arise from seafood and 31% from rice/rice cereals. Of the estimated total arsenic intakes, seafood contributes 76-90% for children (2-10-year olds), 79-85% for 14-16-year olds, and 89-96% for adults (> or = 25-30-year olds); rice/rice cereals contributes 4-8% for children, 8% for 14-16-year olds, and 1-4% for adults (> or = 25-30-year olds).

U.S. Food and Drug Administration perspective of the inclusion of effects of low-level exposures in safety and risk assessment.

A brief overview is provided of some of the general safety and risk assessment procedures used by the different centers of the U.S. Food and Drug Administration (U.S. FDA) to evaluate low-level exposures. The U.S. FDA protects public health by regulating a wide variety of consumer products including foods, human and animal drugs, biologics, and medical devices under the federal Food, Drug, and Cosmetic Act. The diverse legal and regulatory standards in the act allow for the consideration of benefits for some products (e.g., drugs) but preclude them from others (e.g., food additives). When not precluded by statutory mandates (e.g., Delaney prohibition), the U.S. FDA considers both physiologic adaptive responses and beneficial effects. For the basic safety assessment paradigm as presently used, for example in the premarket approval of food additives, the emphasis is on the identification of adverse effects and no observed adverse effect level(s) (NOAEL). Generally, the NOAEL is divided by safety factors to establish an acceptable exposure level. This safety assessment paradigm does not preclude the consideration of effects whether they are biologically adaptive or beneficial at lower dose levels. The flexibility to consider issues such as mechanisms of action and adaptive and beneficial responses depends on the product under consideration. For carcinogenic contaminants and radiation from medical devices, the U.S. FDA considers the potential cancer risk at low exposure levels. This generally involves downward extrapolation from the observed dose-response range. The consideration of adverse effects of other toxicologic end points (e.g., reproductive, immunologic, neurologic, developmental) associated with low exposure levels is also becoming more of a reality (e.g., endocrine disrupters). The evaluation of the biologic effects of low-level exposures to toxic substances must include whether the effect is adverse or a normal physiologic adaptive response and also determine the resiliency of a physiologic system. The public health mandate of the U.S. FDA includes an active research program at the National Center for Toxicological Research and the other U.S. FDA centers to support the regulatory mission of the U.S. FDA. This includes the development of knowledge bases, predictive strategies, and toxicologic studies to investigate effects at the lower end of the dose-response range. Because of the wide diversity of legal and regulatory standards for various products regulated by the U.S. FDA agency-wide safety and risk assessment procedures and policies generally do not exist.

Preliminary assessment of potential health hazards associated with barium leached from glazed ceramicware.

Ceramic glazes contain several elements which have the potential to leach into food or beverages that are held or stored in ceramicware. Recently, barium salts have been investigated as one of the alternatives to lead in frit formulations for glazes. This preliminary evaluation addresses the potential health hazards associated with barium at levels that might leach from glazed ceramicware. A set of specialty ceramicware, consisting of five teacups and a pitcher, was examined for extractable barium. Exposure to barium that adults (18-44 years) might encounter using the vessels for coffee, tea, or orange juice was estimated. The exposure estimate was derived from values for intakes of the beverages and for the barium migration from glazed ceramicware test samples. An established reference dose (RfD) for barium exposure for the critical effect of hypertension was identified. The potential hazard associated with the leaching of barium from glazed ceramicware varied with the level of use. Consuming beverages in amounts up to the 95th percentile would not result in total barium intake in amounts that exceed the RfD; consuming large quantities (> 95th percentile) of beverages such as tea or coffee from glazed vessels might. This suggests that for a small portion of the population of users, intake of barium may be in quantities that warrant further consideration as a potential health hazard. Analyses of a broad sample of ceramicware and study of barium leaching behaviour under actual use conditions are needed to assess further the significance of these findings.

Hazard assessment of germanium supplements.

Germanium-containing dietary supplements became popular in the 1970s in Japan and later in other countries, as elixirs for certain diseases (e.g., cancer and AIDS). Germanium is not an essential element. Its acute toxicity is low. However, at least 31 reported human cases linked prolonged intake of germanium products with renal failure and even death. Signs of kidney dysfunction, kidney tubular degeneration, and germanium accumulation were observed. Other adverse effects were anemia, muscle weakness, and peripheral neuropathy. Recovery of renal function is slow and incomplete even long after germanium intake was stopped. The total dose of ingested germanium (as dioxide, carboxyethyl germanium sesquioxide, germanium-lactate-citrate, or unspecified forms) varied from 15 to over 300 g; the exposure duration varied from 2 to 36 months. In laboratory animals, elevated germanium in tissues and impaired kidney and liver function were observed in a life-time drinking water (5 ppm germanium) study. Other toxicities associated with ingested germanium products in human cases were also demonstrated in animal studies with germanium dioxide and sometimes other germanium compounds. Based on the evidence of persistent renal toxicity associated with germanium dioxide, the lack of conclusive findings of differential nephrotoxicity of organic germanium compounds, and the possibility of contamination of the organic germanium products with inorganic germanium, it is clear that germanium products present a potential human health hazard.

Identification and reduction of sources of dietary lead in the United States.

Lead, an environmental contaminant, originates from a variety of sources. For over two decades, the US Food and Drug Administration (FDA) has made a number of efforts to reduce dietary lead exposure of the general population, and especially of vulnerable subpopulations such as infants and children and, indirectly, the foetus. Through cooperation with infant food manufacturers, reductions of about 80-90% in the lead content of infant foods were achieved, primarily through eliminating the use of cans for infant food products and following good manufacturing practices. Another major reduction in dietary lead was realized by discontinuing the use of lead solder in domestically produced food cans. FDA has also taken steps to minimize or further reduce sources of lead in the diet from lead glazes on ceramicware, leaded crystalware, dietary supplements bottle water, and lead capsules on wine bottles. These actions have resulted in a considerable decrease in the exposure of the United States population to dietary lead.

Risk analysis of dietary lead exposure.

Distribution of intake and lead levels in dietary and non-dietary sources and of lead absorption were used in a Monte-Carlo simulation to predict blood lead levels in populations of concern. Blood lead levels were determined with and without particular dietary sources, and added risk was estimated for each source. These calculations permit comparisons of relative risk used to evaluate and limit dietary exposure to lead. Added risk of exposure to lead in wine, calcium supplements and ceramic-ware, and drinking water were calculated for adult men, pregnant women, and children, respectively.

Hazard assessment of lead.

Exposure to lead (Pb) continues to be a source of concern for the US Food and Drug Administration and other United States federal regulatory agencies. Blood lead levels as low as 10 micrograms/dl have been associated with impaired neurobehavioural and cognitive development and electrophysiological deficits in children and reduced gestational age and birth weight in infants. Blood lead levels of 10 micrograms Pb/dl are also of concern in pregnant women because of exposure to the fetus. Blood lead levels of 30 micrograms Pb/dl have been associated with elevated blood pressure and other adverse effects in adults. Thus, the values of 10 and 30 micrograms Pb/dl represent lowest-observed-effects levels for developing and adult populations, respectively. The ingestion levels that result in these blood levels of concern were estimated to be 60 micrograms Pb/day for children ages 6 years or younger, 150 micrograms Pb/day for children aged 7 years or older, 250 micrograms Pb/day for pregnant women and 750 micrograms Pb/day for adults. Provisional total tolerable intake levels for lead were derived from these blood lead levels for each group by applying the Renwick approach to obtain a tolerable exposure level.

An assessment of the hazards of lead in food.

Exposure to lead (Pb) continues to be a source of concern for the U.S. Food and Drug Administration and other federal regulatory agencies. Blood lead levels as low as 10 micrograms Pb/dl have been associated with impaired neurobehavioral development in children and infants. Because of exposure to the fetus, blood lead levels of 10 micrograms Pb/dl are also of concern in pregnant women. Blood lead levels of 30 micrograms Pb/dl have been associated with elevated blood pressure and other adverse effects in adults. The dietary exposure that results in these blood levels of concern were estimated to be 60 micrograms Pb/day for children age 6 years or younger, 150 micrograms Pb/day for children age 7 years or older, 250 micrograms Pb/day for pregnant women, and 750 micrograms Pb/day for adults. A provisional tolerable total dietary intake was derived by applying a factor of 10 to obtain an exposure level that would include some margin of safety.

Role of FDA in establishing tolerable levels for dioxin and PCBs in aquatic organisms.

When fishery products shipped in interstate commerce contain an environmental contaminant that presents a potential threat to public health, the Food and Drug Administration (FDA) undertakes appropriate regulatory steps to minimize exposure. These efforts range from seizure of the affected product to formal rule-making to establish a limit. The basic provision of the Food, Drug, and Cosmetic (FD&C) Act by which the agency deals with environmental contaminants in the food supply is section 402(a)(1), which deals with poisonous and deleterious substances. Poisonous and deleterious components are deemed to be "added," even if they are natural constituents of food, if any amount is present through the artifice of man. Furthermore, when the level of a naturally occurring toxin is increased in the food through handling and/or processing, the sum of all of the contaminant is deemed to be "added." Unavoidable environmental contaminants may be controlled and/or regulated under this section by the "may render injurious" standard, whereby the agency must demonstrate that there is a significant possibility that exposure to the contaminant could be injurious to human health. "Action levels" are administrative guidelines or instructions to the agency field units that define the extent of contamination at which the agency may regard food as adulterated. Except for polychlorinated biphenyls, for which there is a tolerance established by regulation, FDA has controlled contaminants in aquatic organisms by using action levels. Under section 406 of the FD&C act, the agency can also establish tolerances for unavoidably added poisonous or deleterious substances. This section allows the agency to consider the extent to which a contaminant is unavoidable in food while it limits exposure to the extent necessary to protect the public health. Section 406 requires that the tolerance be established by assessing several factors, including risk. One of these is the capability of processing technology to prevent, reduce, or otherwise control the level of the contaminant. Another factor is the necessity to avoid the needless removal of large amounts of valuable food from the market. Finally, the available analytical and sampling methods must be capable of measuring the contaminant so as to ensure the enforceability of the tolerance. Although the FDA has no statutory authority over intrastate fishing considerations, such as noncommercial fishing, it does provide advice to local or state authorities. It is the best scientific opinion the agency can give, but it is not enforceable per se. Advice is provided when requested by local and state officials where no guideline or tolerance is available, and is meant to deal with local and/or regional public health concerns.(ABSTRACT TRUNCATED AT 400 WORDS)