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PubMed2007

Refinements on the age-dependent half-life model for estimating child body burdens of polychlorodibenzodioxins and dibenzofurans.

We modified our prior age-dependent half-life model to characterize the range of child (ages 0-7) body burdens associated with dietary and environmental exposure to polychlorodibenzodioxins and furans (PCDD/Fs). Several exposure scenarios were evaluated. Infants were assumed to be either breast-fed or formula-fed from birth to 6 months of age. They then received intakes of PCDD/Fs through age 7 from foods based on weighted means estimates [JECFA, 2001. Joint FAO/WHO Committee on Food Additives. Fifty-seventh meeting, Rome, June 5-14 , 2001, pp. 24-40], and with or without exposures (ingestion and dermal) to urban residential soils at 1ppb TCDD toxic equivalents (TEQ). A one-compartment (adipose volume) toxicokinetic model for TCDD described by Kreuzer [Kreuzer, P.F., Csanady, Gy.A., et al., 1997. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch. Toxicol. 71, 383-400] was expanded to include the key non-TCDD congeners in human breast milk and adipose tissues, and two model parameter refinements were examined: (1) use of updated and more detailed age-correlated body fat mass data [CDC, 2000. Centers for Disease Control. CDC Growth Charts: United States. Advance Data from Vital and Health Statistics of the Centers for Disease Control and Prevention, National Center for Health Statistics, Number 314, December 2000]; (2) use of breast milk PCDD/F concentration data from sampling completed in 2000-2003 [Wittsiepe, J., Fürst, P., et al., 2004. PCDD/F and dioxin-like PCB in human blood and milk from German mothers. Organohalogen Compd. 66, 2865-2872]. The updated body fat mass data nearly halved the predicted peak body burden for breast-feeding and lowered the time-weighted average (TWA) body burdens from ages 0-7 by 30-40% for breast-fed and formula-fed infants. Combined use of the updated breast milk PCDD/F concentration and body fat mass data increased the contribution of breast-feeding but reduced TWA body burdens from diet and soil. We conclude that further refinements are needed, but reliance on these better data sets for body fat mass and breast milk PCDD/F concentration significantly improves the model's ability to accurately predict body burdens during early childhood.

Adipose Tissue↗
PubMed2000

Methodology for characterizing distributions of incremental body burdens of 2,3,7,8-TCDD and DDE from breast milk in North American nursing infants.

A clear picture of ranges of doses of breast-milk contaminants experienced by nursing infants in North America has not yet been described, resulting in a significant gap in our understanding of potential health risks to infants from those contaminants. While point estimates of incremental dose have appeared in the published literature, these do not account for the wide variability in exposures experienced by nursing infants. This research expands on the current state of understanding of breast-milk contaminant exposure by characterizing distributions, rather than point estimates, of dose. Distributions of milk intake by nursing infants were characterized to examine intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and dichlorodiphenyl dichloroethane (DDE). The results indicate that, despite the uncertainties inherent in modeling incremental body burdens of chemicals from nursing, estimating incremental infant body burdens of lipophilic chemicals from breastfeeding using point estimates may result in overly conservative estimates of the contribution of breastfeeding to long-term body burdens of those chemicals in children. To develop reliable estimates of incremental body burden from nursing, depuration via lactation and half-life in the infant should be considered. Further, incremental infant body burdens of lipophilic chemicals increase rapidly at the start of lactation, but decrease after approximately 5 to 6 mo; by 2 yr postpartum, incremental body burdens have decreased substantially. Given the benefits afforded to infants who breastfeed, and because breastfeeding does not necessarily lead to significantly increased long-term body burdens in infants, breastfeeding should be encouraged and promoted.

Body Burden↗
PubMed1990

Human body burden of polychlorinated dibenzofurans associated with toxicity based on the yusho and yucheng incidents.

The polychlorinated dibenzofurans (PCDFs) are one group of man-made toxicants for which reasonably extensive data exist relevant to dose-response relationships in humans. Examination of contaminated food oil consumption from the yusho (Japan) poisoning incident indicates the mean uptake or body burden of 2, 3, 4, 7, 8-pentachlorodibenzofuran (PnCDF) equivalents (PEQ) associated with nausea and anorexia to be 4.4 micrograms/kg body wt and that associated with chloracne to be 5.9 micrograms/kg. For the yucheng (Taiwan) poisoning incident, blood measurements for chloracne show a similar body burden of 4.0 micrograms/kg. The latter value is toxicologically equivalent to a 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ) body burden of 2.0 micrograms/kg body wt or about 150 micrograms for an adult person. This corresponds to an adipose tissue level of about 10 micrograms/kg fat, and is comparable to that known to cause chloracne in rhesus monkeys. These body burdens on a TEQ basis are more than 200 times higher than the average current levels of PCDDs/PCDFs found in North American populations and are the first to relate human body burdens of PCDFs with a known effect and to compare them to animal data. Since the effects reported may not be the most sensitive indicator of human toxicity, lower body burdens could be associated with more subtle toxicological events.

Adolescent↗
PubMed2005

Does long term residency near industry have an impact on the body burden of polychlorinated dibenzo-p-dioxins, furans, and polychlorinated biphenyls in older women?

BACKGROUND: For the retrospective study of environment and health linkages biomarkers of exposure are required. Polychlorinated dibenzo-dioxins and furans (PCDD/F) and polychlorinated biphenyls (PCBs) have been useful markers in some settings. This is the first study of PCDD/F body burden in a population based sample from the UK. AIMS AND METHODS: The authors aimed to investigate whether long term residents close to a heavy chemical industrial complex (Teesside, UK) had a higher body burden and distinct pattern of PCDD/F and PCBs. We measured current levels of PCDD/F and PCBs in a population based sample of older women (mean 64 years, range 42-79 years). Forty women were recruited, 20 living near (zone A: 0.1-2.7 km) and 20 distant (zone C: 5-40 km) from industry during 2000-03. The authors ascertained occupational exposure to lung carcinogens, residential history, consumption of local produce, breast feeding, diet, and height and weight. RESULTS: The mean body burden measured on lipid basis in ng/kg for the whole sample was: WHO-TEQ (PCDD/Fs): 29.9, 2378TCDD: 4.0, PCB 118:16200, PCB156: 13100. Body burdens were similar to others reported from industrialised countries, except that mean 2378TCDD was slightly higher. Mean ages, body mass index, and lifelong dietary patterns were similar in both zones. The authors found no significant difference in mean body burden levels between zones A and C before or after adjustment for covariates. All congener patterns were consistent with an urban background pattern, and there was no significant difference between congener compositions in the two zones. The TCDD body burden increased with age with accelerated increments above age 70. CONCLUSION: Long term residency near heavy and chemical industry did not have an effect on women's body burden of PCDD/Fs and PCBs on Teesside, UK. The body burden of PCDD/F and PCBs was not a suitable biomarker for chronic, non-occupational exposure to industrial air pollution.

Aged↗
PubMed1997

Radiocesium body burdens in residents of northern Canada from 1963-1990.

Measurements of 137Cs body burdens in over 1,100 people from five northern Canadian communities were carried out with a portable whole body counting system during the winters of 1989 and 1990. These results are compared with over 3,000 similar measurements carried out during 1967-1969. Community mean body burdens and body concentrations had decreased by approximately a factor of 30 between the two survey periods. The dependence of body concentrations on the sex and age of the subjects has also changed significantly. This can be related to changes in the patterns of caribou consumption in the northern communities. Measurements of 137Cs in urine are also available for an earlier period (1963-1966) when world-wide fallout was at its highest level. A normalization procedure was developed to calculate the average radiocesium body concentration in each community from the concentrations in urine. From data spanning a period of nearly 30 y (1963-1990), lifetime radiation doses have been estimated for most communities in the Yukon and Northwest Territories. These cumulative doses vary from 0.3 to nearly 40 mSv, with an Arctic-wide average of about 12 mSv. No health effects would be expected at these levels.

Adolescent↗
PubMed1995

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system. 2. In vitro proliferation of lymphocytes from workers with quantified moderately-increased body burdens.

Lymphocyte proliferation responses were studied in workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin and other polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs, calculated as International Toxicity Equivalencies [I-TE]). Mitogens (pokeweed mitogen [PWM], phytohemagglutinine [PHA], concanavalin A [Con A]), as well as an anti-human monoclonal antibody against CD3 were used as proliferation stimulators in vitro. Additionally, the feasibility of using the lymphocyte response to tetanus toxoid was assessed, and the response to this recall-antigen was included in this trial. No decrease in the capacity of 3H-thymidine incorporation was observed with any of the proliferation stimulators in the group of volunteers with the increased TCDD-body burden when compared with volunteers exhibiting TCDD-concentrations in blood fat within the reference range. Regression analysis revealed a slight trend towards an increase for 3H-thymidine incorporation during the stimulation with PHA only. It can be concluded from our data that moderate increases in the TCDD- or I-TE-body burdens do not induce any medically significant changes in the capacity for proliferation of lymphocytes, measured as 3H-thymidine incorporation.

Adult↗
PubMed1982

Assessment of the body burden of chelatable lead: a model and its application to lead workers.

A hypothetical model was introduced to estimate the body burden of chelatable lead from the mobilisation yield of lead by calcium disodium ethylenediamine tetra-acetate (CaEDTA). It was estimated that, on average, 14 and 19% of the body burden was mobilised into the urine during the 24 hours after an injection of 53.4 mumol (20 mg) and 107 mumol (40 mg) CaEDTA per kg bodyweight, respectively. The body burden of chelatable lead ranged from 4 mumol (0.8 mg) to 120 mumol (24.9 mg) (mean 37 mumol (7.7 mg) in lead workers with blood lead concentrations of 0.3-2.9 mumol/kg (6-60 microgram/100 g) (mean 1.4 mumol/kg (29 microgram/100 g)). There were linear relationships between blood lead concentrations and body burden of chelatable lead on a log scale.

Adult↗
PubMed1991

A time-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin body-burden model.

Estimates of the 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) body-burden acquired from an environment in which 2,3,7,8-TCDD has been introduced in a high concentration, are derived from an idealized linear reaction kinetic model. The model parameters are the 2,3,7,8-TCDD transfer factor from the environmental soil medium to the human body, the background intake, the soil concentration and the body and soil elimination half-times. Values of the transfer factor are estimated from reported human and environmental data. The model conservatively determines a time-scale over which the acquired body-burden may be significantly higher than the background dose caused by the ubiquitous presence of 2,3,7,8-TCDD in food, consumer products, etc. and allows comparison of the cumulative body-burden with published values for the minimum toxic dose and derived values of the minimum guideline dose. The linear nature of the model also provides a framework for the estimation of the 2,3,7,8-TCDD toxic equivalent (TEQ) body-burden acquired from environments in which a mixture of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are present.

Body Burden↗
PubMed2001

Testing of metal bioaccumulation models with measured body burdens in mice.

Estimates of chemical accumulation in prey organisms can contribute considerable uncertainty to predictive ecological risk assessments. Comparing body burdens calculated in food web models with measured tissue concentrations provides essential information about the expected accuracy of risk indices. Estimates of arsenic, cadmium, copper, lead, and nickel body burdens in house mice (Mus musculus) inhabiting a seasonal wetland were generated with two small mammal bioaccumulation models. Published soil-to-small mammal bioaccumulation regression models produced accurate estimates of arsenic and lead body burdens but failed to adequately predict copper and nickel levels in mice. Incorporating conservative prediction intervals in the regression models shows potential for successful applications in screening-level risk assessments. A simple mechanistic cumulative ingestion bioaccumulation model overpredicted lead levels in mice generally by less than one order of magnitude but greatly overpredicted concentrations of arsenic, copper, and nickel. Better estimates of absorption and elimination of ingested metals and knowledge of specific arthropod taxa in house mouse diets are likely to improve the accuracy of the cumulative ingestion model. Applying Monte Carlo simulations to the soil-small mammal regression models generated probabilistic estimates of body burdens that were consistent with deterministic results. However, deterministic minimum and maximum predictions of the ingestion model were excessively conservative (widely spaced) relative to lower and upper probabilistic percentiles. Metal levels predicted in individual mice on the basis of mouse-specific parameter values and exposures were not significantly more accurate than bioaccumulation predictions for the sitewide population.

Animals↗
PubMed1995

Radiocesium body burdens in immigrants to Israel from areas of the Ukraine, Belarus and Russia near Chernobyl.

Of the 500,000 immigrants from the former Soviet Union who came to Israel during 1990-1993, about 100,000 are estimated to have come from radiocontaminated areas near Chernobyl. These people were subject to chronic uptake of environmental radiocesium over protracted periods. During October-November 1991, a joint Israeli-Canadian investigation measured radiocesium body burdens in immigrants to Israel from the Ukraine, Belarus, and the southern Russian republic in order to provide factual information on radiocesium levels to concerned immigrants and to relate the body burdens to the geographic area of residence before coming to Israel. Assessments were made of 137Cs body burdens in 1,228 volunteer men, women, and children. These measurements were accompanied by medical assessments based on clinical histories and examinations. Radiocesium levels were strongly dependent on the duration of residence in Israel, with the highest levels being found in the most recent immigrants. The maximum level, extrapolated back to the time of leaving the former Soviet Union, was estimated to be about 0.83 kBq (10.3 Bq kg-1). Of the most recent immigrants from the Kiev region (< 101 days in Israel), only 15% had back extrapolated body burdens > 50 Bq, whereas 53% of those coming from Gomel and other towns in the contaminated zones (> 3.7 x 10(10) Bq km-2 of radiocesium) had detectable levels > 50 Bq. People coming from the latter region had significantly higher body burdens as compared to those from the former, in accordance with the higher degree of ground radiocesium contamination reported for the latter region. Women and children showed considerably lower total radiocesium content in comparison to men. All radiocesium body burdens at the time of measurement were too low to be of health concern.

Adolescent↗
PubMed1990

Total body burdens and tissue concentrations of lead, cadmium, copper, zinc, and ash in 55 human cadavers.

Trace metal contents of human tissues and total body burdens are useful for studies of nutrition and certain diseases. Data are summarized and analyzed for individuals exposed to the normal Cincinnati environment, for 29 tissues from 55 cadavers for lead and ash concentrations, and from 26 cadavers for cadmium, copper, and zinc concentrations. Total body burdens also were calculated and correlated against each other and age. The distributions for ash, copper, and zinc were close to normal, but those for lead and cadmium were closer to lognormal. Bone lead increased with age, whereas soft tissue lead did not. The calculated mean percentage of total body lead in the bones ranged from 78% at age 20 to 96% at age 80. Correlations of blood concentrations with total body burdens were negligible for cadmium and zinc. For copper the correlation coefficient was a poor 0.54. For lead in blood vs soft tissue burden it was a very poor 0.37, and vs total body lead it was negligible. Thus the use of blood samples as a convenient clinical measure of body burdens for these metals may be of limited value. These and other findings provide a useful bank of information for health studies.

Adult↗
PubMed1993

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system. 1. Blood cell receptors in volunteers with moderately increased body burdens.

Using monoclonal antibodies (mAbs) and flow cytometry, we studied a variety of surface receptors on lymphocyte subpopulations of workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of other polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), expressed here as International-Toxicity Equivalencies (I-TE). The hypothesis to be tested was whether or not humans exhibit a similar susceptibility to PCDDs/PCDFs with respect to the surface receptors found previously to respond to small doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Callithrix jacchus. These are: helper-inducer (memory) T cells (CD4+CD45R0+CD45RA-CD29highCD11a+), CD20+ B cells, and cytotoxic T cells (CD8+CD56+/CD57+). Furthermore, 68 triple-labellings with mAbs were performed on the cells of each volunteer to possibly generate further hypotheses. It was evaluated whether any of the variables might be used as a biomarker of effects for this class of compounds. There were two main goals: (1) to evaluate whether workers with a moderately increased PCDD/PCDF-body burden [25-140 ppt TCDD or 104-522 ppt I-TE in blood fat] exhibit changes in the surface receptors of white blood cells, as observed in previous studies in non-human primates, and (2) to clarify whether persons at the upper range [10-23 ppt TCDD or 30-90 ppt I-TE in blood fat] of the body burden reference values of a not particularly exposed population show detectable deviations in these immunological variables, when compared with persons at the lower and medium range [1-3 ppt TCDD or 9-29 ppt I-TE] of these body burden reference values. Regression analysis of our data revealed slight trends for some of the biomarkers (e.g. CD45R0+). With one exception, these were all increases. None of the alterations observed are of medical relevance. The slight increase in the percentage of CD4+CD45R0+ cells remained significant even after covariant analysis taking age-related changes into account. Altogether, the data do not provide any evidence to support an assumption that moderately increased body burdens of PCDDs/PCDFs in adults induce decreases in the cellular components of the human immune system. Adult humans certainly are less susceptible to this action of PCDDs/PCDFs than adolescent Callithrix jacchus.

Adult↗
PubMed1959

Maximum permissible body burden of strontium-90.

The permissible body burden of Sr(99) is discussed with respect to the mode of intake. It appears that the maximum permissible load may depend on the type of exposure, acute or chronic, the acute being the more serious.

Body Burden↗
PubMed1992

Assessment of accumulated body burden of metals.

Knowledge of the body burden of a metal is important for evaluation of exposure and risk. Traditionally, the burden has been estimated through levels in blood, urine, hair, or shed teeth, or by mobilization tests. However, all these methods have limitations. In vivo methods for determination of cadmium in kidney by neutron activation analysis or X-ray fluorescence (XRF) reflect the burden, long-term exposure, and risk of toxic effect. In vivo determination by XRF of lead in fingerbone, tibia, or calcaneus reflect the long-term exposure, and should become a valuable tool in epidemiological studies, especially of chronic effects.

Body Burden↗
PubMed1980

A comparison of methods for assessing patient body burden following 131I therapy for thyroid cancer.

The effectiveness of three methods of assessing the patient body burden following 131I therapy was compared: (a) urine assay, (b) external exposure rate measurements, and (c) predictions based on a pretherapy diagnostic work-up. The urine assay method exhibited the greatest potential for error and personnel risk. The diagnostic work-up provided predictions of the body burden as a function of time, which may be applied to estimate the expected hospital stay. The direct external exposure rate survey showed the potential for being an accurate, reliable, and relatively safe method of monitoring the patient body burden.

Body Burden↗
PubMed2006

Relative cancer potencies of selected dioxin-like compounds on a body-burden basis: comparison to current toxic equivalency factors (TEFs).

Recent National Toxicology Program (NTP) cancer bioassay data for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and a mixture of these three compounds offer opportunities to assess the accuracy of current World Health Organization (WHO) 1998 toxic equivalency factors (TEFs) for these compounds under a variety of assumptions. An evaluation of the current TEF values for these compounds using body burden in nanograms per kilogram as the dose metric is presented. Average lifetime body burdens were estimated for all compounds at all dose groups based on measured tissue concentrations at 4 time points during the 2-yr NTP studies. Poly-3 adjusted tumor incidences for hepatocellular adenomas, cholangiocarcinomas, and the two tumors combined were modeled using a quantal multistage model and the Hill model with lifetime average body burden as the dose metric. Benchmark doses for a 10% response (BMD10) for each compound and the mixture were estimated. With TCDD as the reference standard, relative potency (REP) estimates were derived from ratios of the BMD10 estimates for PCB 126, 4-PeCDF, and for the toxic equivalent (TEQ) mixture. On a body-burden basis, PCB 126 and 4-PeCDF were 2- to 3-fold and 10- to 12-fold less potent than predicted based on the WHO TEFs, respectively, while the TEQ mixture was approximately 3- to 5-fold less potent than predicted by the TEFs. The current WHO TEF values, which were derived from data on noncancer endpoints evaluated on an administered dose basis, overpredict the carcinogenic potency of these compounds on a body-burden basis compared to TCDD.

Adenoma, Liver Cell↗
PubMed2001

The geographic distribution of population health and contaminant body burden in gulf of Mexico oysters.

As part of NOAA's National Status and Trends Mussel Watch Program, oysters were sampled along the Gulf of Mexico coast each winter from 1986 to 1993 (The present analysis deals with 1986-1993 Mussel Watch data; the Mussel Watch project itself continues at this printing) and analyzed for trace metal, polynuclear aromatic hydrocarbons and pesticide body burden, plus a series of biological variables designed to assess population status and health. We identified contaminant and biological variables in which large-scale spatial processes played an important role in establishing population values by examining the likelihood that neighboring bays tended to have populations with body burdens or population attributes more similar than expected by chance. Local or watershed-dependent factors, such as land use and freshwater inflow, are important in controlling the bay-to-bay variation in body burden in most contaminants. However, the bay-to-bay variations in body burden of some metals (As, Cd, Hg, Ni, Se) appear to be principally influenced by larger-scale climatic factors. These metals and the biological variable shell length demonstrated a strong degree of similarity between bays over a large regional area reminiscent of the pattern shown by climatic factors, such as temperature and precipitation. In contrast, among the organics, none of the PAHs showed even a moderately strong climatic signal. Among the pesticides, only two did (dieldrin, total DDTs). These pesticides and the biological variables, reproductive stage and Perkinsus marinus prevalence and infection intensity, had spatial patterns that suggested both a local and a regional influence to their geographic distributions. This same pattern is exhibited by freshwater runoff. Metal contaminants also behaved distinctively compared to organics in the temporal influence of climate in establishing the interannual variability in body burden. For the organics, trends in interannual variability were strongly influenced by climate, whereas spatial trends were not. In contrast, most metals were unaffected by climatic forcing both spatially and temporally. However, all of the metals having a spatial pattern strongly influenced by climate (As, Cd, Hg, Ni, Se) also exhibited interannual variations related to variations in climate.

Animals↗
PubMed2002

Polycyclic aromatic hydrocarbon bioaccumulation by meiobenthic copepods inhabiting a superfund site: techniques for micromass body burden and total lipid analysis.

Microtechniques for polycyclic aromatic hydrocarbon (PAH) body burden and total lipid analysis were developed and applied to determine the first lipid-normalized bioaccumulation factors for a hydrophobic organic toxicant in a meiobenthic organism (0.063-0.500 mm) living in field-contaminated sediments. The total lipid microtechnique combines the standard Bligh-Dyer extraction method with a colorimetric quantification method for analysis of samples containing I to 50 microg lipid. The microtechnique for body burden analysis quantifies PAHs from tissue samples containing as little as 10 pg PAH. Fluoranthene, benz[a]anthracene, and benzo[a]pyrene biota-sediment accumulation factors (BSAFs) were determined for the meiobenthic copepod Microarthridion littorale living in an estuarine U.S. Environmental Protection Agency Superfund site. Gravid female, nongravid female, and male BSAFs were 0.82, 0.54, and 0.36, respectively, for fluoranthene; 0.50, 0.44, and 0.40, respectively, for benz[a]anthracene; and 0.09, 0.12, and 0.15, respectively, for benzo[a]pyrene. Comparison of nonlipid-normalized bioaccumulation factors (BAFs) to BSAFs indicates that M. littorale bioaccumulated PAHs on a gram lipid basis. The BSAFs declined consistently with increasing PAH log K(ow) for all copepod sex and reproductive stages. Sex- and stage-specific comparisons of BSAFs suggest that differences in lipid content and quality may lead to differences in BSAF values depending on PAH molecular weight and/or hydrophobicity.

Animals↗