BackgroundIn recent decades, young men in some industrialized areas have reportedly experienced a decrease in semen quality.ObjectiveWe examined effects of perinatal dioxin exposure on sperm quality and reproductive hormones.MethodsWe investigated sperm quality and hormone concentrations in 39 sons (mean age, 22.5 years) born between 1977 and 1984 to mothers exposed to dioxin after the accident in Seveso, Italy (1976), and 58 comparisons (mean age, 24.6 years) born to mothers exposed only to background dioxin. Maternal dioxin levels at conception were extrapolated from the concentrations measured in 1976 serum samples.ResultsThe 21 breast-fed sons whose exposed mothers had a median serum dioxin concentration as low as 19 ppt at conception had lower sperm concentration (36.3 vs. 86.3 million/mL; p = 0.002), total count (116.9 vs. 231.1; p = 0.02), progressive motility (35.8 vs. 44.2%; p = 0.03), and total motile count (38.7 vs. 98 million; p = 0.01) than did the 36 breast-fed comparisons. The 18 formula-fed exposed and the 22 formula-fed and 36 breast-fed comparisons (maternal dioxin background 10 ppt at conception) had no sperm-related differences. Follicle-stimulating hormone was higher in the breast-fed exposed group than in the breast-fed comparisons (4.1 vs. 2.63 IU/L; p = 0.03) or the formula-fed exposed (4.1 vs. 2.6 IU/L; p = 0.04), and inhibin B was lower (breast-fed exposed group, 70.2; breast-fed comparisons, 101.8 pg/mL, p = 0.01; formula-fed exposed, 99.9 pg/mL, p = 0.02).ConclusionsIn utero and lactational exposure of children to relatively low dioxin doses can permanently reduce sperm quality.

Perfluorooctanoic acid (PFOA) is a persistent chemical that was recently shown to be widely distributed in the ambient environment. Because of concerns about the possible adverse health effects on persons exposed to PFOA, a retrospective exposure assessment was conducted for a population of about 50,000 persons who reside near one of the facilities where this chemical was used. No similar study of any chemical with the properties of PFOA had ever been performed; thus, several novel methods were developed and applied in this analysis. Historical records of the emissions from the facility were the basis for the estimates of the potential intake of (PFOA) by residents over the past 53 yr. Various well-accepted environmental models were dynamically combined in order to estimate the concentrations in all relevant environmental media including ambient air, surface soil, drinking water, and homegrown vegetables. Following considerable analyses, particulate deposition from facility air emissions to soil and the subsequent transfer of the chemical through the soil was determined to be the most likely source of PFOA that was detected in groundwater. The highest off-site environmental concentrations were predicted to occur about 1 mile away. For this approximately square mile area, during the time period 1951-2003, the model-estimated average air concentration was 0.2 microg/m3, the estimated surface soil concentration was 11 microg/kg, and the estimated drinking water concentration was 4 microg/L. Similar data were generated for 20 additional geographical areas around the facility. Comparison of measured PFOA concentrations in groundwater in the various water districts indicated that the models appeared to overpredict recent groundwater concentrations by a factor of 3 to 5. The predicted historical lifetime and average daily estimates of PFOA intake by persons who lived within 5 miles of the plant over the past 50 yr were about 10,000-fold less than the intake of the chemical not considered as a health risk by an independent panel of scientists who recently studied PFOA.

Although there has been nearly complete agreement in the scientific community that Monte Carlo techniques represent a significant improvement in the exposure assessment process, virtually all state and federal risk assessments still rely on the traditional point estimate approach. One of the rate-determining steps to a timely implementation of Monte Carlo techniques to regulatory decision making is the development of "standard" data distributions that are considered applicable to any setting. For many exposure variables, there is no need to wait any longer to adopt Monte Carlo techniques into regulatory policy since there is a wealth of data from which a robust distribution can be developed and ample evidence to indicate that the variable is not significantly influenced by site-specific conditions. In this paper, we propose several distributions that can be considered standard and customary for most settings. Age-specific distributions for soil ingestion rates, inhalation rates, body weights, skin surface area, tapwater and fish consumption, residential occupancy and occupational tenure, and soil-on-skin adherence were developed. For each distribution offered in this paper, we discuss the adequacy of the database, derivation of the distribution, and applicability of the distribution to various settings and conditions.

ObjectivePharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents.DesignWe used blood concentrations to calculate TCDD elimination half-life. Variables examined by statistical analysis include age, latency from exposure, sex, TCDD concentration and quantity in the body, severity of chloracne response, body mass index, and body fat mass.ParticipantsBlood was collected from 1976 to 1993 from residents of Seveso, Italy, who were < 18 years of age at the time of a nearby trichlorophenol reactor explosion in July 1976.ResultsTCDD half-life in persons < 18 years of age averaged 1.6 years while those ≥18 years of age averaged 3.2 years. Half-life is strongly associated with age, showing a cohort average increase of 0.12 year half-life per year of age or time since exposure. A significant concentration-dependency is also identified, showing shorter half-lives for TCDD concentrations > 400 ppt for children < 12 years of age and 700 ppt when including adults. Moderate correlations are also observed between half-life and body mass index, body fat mass, TCDD mass, and chloracne response.ConclusionsChildren and adolescents have shorter TCDD half-lives and a slower rate of increase in half-life than adults, and this effect is augmented at higher body burdens.RelevanceModeling of TCDD blood concentrations or body burden in humans should take into account the markedly shorter elimination half-life observed in children and adolescents and concentration-dependent effects observed in persons > 400–700 ppt.

We analyzed the weighted 2001-2002 National Health and Nutrition Examination Survey data to assess potential differences in mean total 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) TEQ between various groups of individuals and to determine serum reference concentrations for polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs) in the general US population. Differences appeared to exist between female smokers and non-smokers and between non-Hispanic groups and all other races. Potential differences were also observed among the four age groups with an increasing trend in mean total TCDD TEQ with increasing age. Both age and gender appeared to confound the association between smoking status and total TCDD TEQ, dictating the need for further analysis. As anticipated, PCBs contributed appreciably to the total TCDD TEQ levels in the referent population and accounted for 38% to 41% of the total TEQ depending on age. Nearly 80% of the mean total TCDD TEQ was attributable to four PCDD/F congeners and three PCB congeners. In this analysis, two methods were used to assess samples where the concentrations were below the limits of detection (LODs), and this did not have significant impact on the mean total TCDD TEQ at the higher percentiles and for older individuals. Comparison of our results to those from a recent PCDD/F biomonitoring study indicates that the mean TCDD TEQ serum concentration of the individuals studied does not appear to be different from typical levels found in the general US population. Additionally, an assessment of data from the National Human Adipose Tissue Survey using our referent statistics shows that levels of these chemicals have been declining in the general population for at least two decades. The reference TEQs presented in this paper provide relevant, current data that can be used to evaluate biomonitoring results of individuals or groups exposed or potentially exposed to PCDD/Fs and PCBs above referent levels.

It has recently been suggested that "standard" data distributions for key exposure variables should be developed wherever appropriate for use in probabilistic or "Monte Carlo" exposure analyses. Soil-on-skin adherence estimates represent an ideal candidate for development of a standard data distribution: There are several readily available studies which offer a consistent pattern of reported results, and more importantly, soil adherence to skin is likely to vary little from site-to-site. In this paper, we thoroughly review each of the published soil adherence studies with respect to study design, sampling, and analytical methods, and level of confidence in the reported results. Based on these studies, probability density functions (PDF) of soil adherence values were examined for different age groups and different sampling techniques. The soil adherence PDF developed from adult data was found to resemble closely the soil adherence PDF based on child data in terms of both central tendency (mean = 0.49 and 0.63 mg-soil/cm2-skin, respectively) and 95th percentile values (1.6 and 2.4 mg-soil/cm2-skin, respectively). Accordingly, a single, "standard" PDF is presented based on all data collected for all age groups. This standard PDF is lognormally distributed; the arithmetic mean and standard deviation are 0.52 +/- 0.9 mg-soil/cm2-skin. Since our review of the literature indicates that soil adherence under environmental conditions will be minimally influenced by age, sex, soil type, or particle size, this PDF should be considered applicable to all settings. The 50th and 95th percentile values of the standard PDF (0.25 and 1.7 mg-soil/cm2-skin, respectively) are very similar to recent U.S. EPA estimates of "average" and "upper-bound" soil adherence (0.2 and 1.0 mg-soil/cm2-skin, respectively).

The oxygenate methyl tertiary butyl ether (MTBE) has been added to reformulated gasoline in the U.S. to meet national ambient air quality standards. Although MTBE has provided significant health benefits in terms of reduced criteria and toxic air pollutants, detections of MTBE in some groundwater and drinking water sources have raised concerns about potential environmental contamination and human exposures. In this paper, we examine the frequency and concentration of MTBE detections in drinking water sources in California from 1995 to 1999, and provide a preliminary analysis of the distribution of household exposures to MTBE from water-related activities. Using published data on the toxicity and possible cancer hazard posed by MTBE, we estimate the likely cancer and non-cancer risks for the general population in California from past and potential future MTBE exposures. More highly exposed subgroups were also addressed. Our findings indicate that less than 2% of all sampled drinking water sources in California had detectable levels of MTBE in 1999, with average MTBE drinking water concentrations ranging from 0.09 to 4.9 ppb for this year. Both the detection rate for MTBE and average MTBE concentrations have remained relatively stable since 1995, despite increased sampling of drinking water sources in California. The probabilistic exposure analysis suggests that drinking water exposures to MTBE are unlikely to pose a significant health risk for the general population or more highly exposed individuals in California.

Toxic equivalency factors (TEFs) for 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs) and coplanar polychlorinated biphenyl (PCB) congeners have been developed by the World Health Organization (WHO). Each TEF was derived from a range of relative potency (REP) estimates obtained from in vivo and in vitro studies wherein the potency of the congener was evaluated relative to 2,3,7,8-TCDD (or some other appropriate benchmark). For most congeners, the range of REP values spans several orders of magnitude, and the degree of conservatism varies widely among the congeners. Although some TEFs are greater than the maximum REP value, others are less than the minimum. This suggests that the point estimate TEFs introduce a significant amount of variability and uncertainty into the PCB and PCDD/F risk assessment process. The use of REP data distributions, rather than point estimate TEFs, would permit a more informed evaluation of the variability and uncertainty in the attendant risk estimates. Further, a standardized method of choosing a TEF from an REP distribution would ensure a uniform degree of conservatism in the TEF values. In this analysis, distributions of REP values were derived for the coplanar PCBs and 2,3,7,8-substituted PCDD/Fs. There are 936 REP values in the WHO database; the number of values per congener ranges from 1 (1,2,3,7,8,9-HxCDF) to 117 (PCB126). Twenty REP values qualified by WHO as "<" were replaced with one-half the stated value; 65 values qualified as ">" were not used. Fit tests indicate that most distributions are lognormal. Mean, standard deviation, and 50th and 95th percentile values for each REP distribution are presented. In general, the WHO TEFs for the PCDD/Fs are at the upper bound (75th percentile or greater) of the underlying REP distributions, while the PCB TEFs tend to be more representative of the central tendency of the underlying REP distribution. A simplistic weighting scheme that emphasizes long-term in vivo studies suggests that the REP distributions may not be overly sensitive to weighting techniques--that is, the statistical descriptors of the weighted distributions were similar to those of the unweighted distributions. A case study using fish tissue PCB and PCDD/F data suggests that in some settings the use of WHO TEFs may understate upper bound PCB risks relative to PCDD/F risks. A preliminary sensitivity analysis suggests that measurement endpoint, tissue-type and species (or strain) may be significant contributors to the variability and heterogeneity in the underlying REP data for some congeners. Although there are fundamental shortcomings inherent in any TEF scheme, evidence suggests that some form of REP distributions should be used in lieu of or in addition to point estimate TEFs in settings where PCBs and PCDD/Fs are commingled.