Predictors of serum dioxin levels among adolescent boys in Chapaevsk,Russia: A cross-sectional pilot study

Background

Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited.

Methods

Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample.

Results

Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundability was reduced among couples from Kharkiv [adjusted fecundability ratio (FR) 0.64 (95% CI 0.5–0.8)] and elevated in Swedish fishermen families [FR 1.26 (95% CI 1.0–1.6)]. Adjusted geometric means of sperm counts and morphology did not differ between regions while sperm motility was higher in men living in Warsaw.

Conclusion

We observed regional differences in time to pregnancy and sperm motility that may be related to regional differences in POP blood levels, but other interpretations are also plausible. In particular, differences in access to safe contraception and in the prevalence of contraceptive failures are most likely to bias comparisons of time to pregnancy.     

Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia: a cross-sectional pilot study

Background  

Toxicological studies and limited human studies have demonstrated associations between exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) and adverse developmental and reproductive health effects. Given that children may be particularly susceptible to reproductive and developmental effects of organochlorines, and the paucity of information available regarding childhood exposures to dioxins in particular, we undertook a pilot study to describe the distribution of, and identify potential predictors of exposure to, dioxin-like compounds and dioxins among adolescent boys in Chapaevsk, Russia. The pilot study was also designed to guide the development of a large prospective cohort study on the relationship of exposure to PCDDs, PCDFs, and PCBs with growth and pubertal development in peri-pubertal Chapaevsk boys.     

Food as a source of dioxin exposure in the residents of Bien Hoa City,Vietnam

Recently, elevated dioxin levels, over 5 parts per trillion (ppt) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), from Agent Orange was reported in 95% of 43 selected residents of Bien Hoa City, a city in southern Vietnam near a former air base used for Agent Orange-spraying missions. Agent Orange herbicide, contaminated with TCDD, was sprayed in Vietnam between 1962 and 1971 primarily for use as a defoliant. Typical blood TCCD levels are 2 ppt in Vietnamese, but levels are as high as 413 ppt in Bien Hoa City. Elevated TCDD was found in children born many years after Agent Orange spraying ended and in immigrants from non-Agent Orange-sprayed parts of Vietnam, which documented new exposures. Extremely elevated soil TCDD samples, over 1 million ppt, and elevated TCDD in sediment were found in some nearby areas such as Bien Hung Lake. The primary route of intake of almost all dioxins in humans is food. However, in our prior studies in Bien Hoa, food was unavailable for dioxin analysis so the route of intake was not confirmed. In the 1970s, while Agent Orange was still being sprayed, elevated human milk TCDD levels as high as 1850 were detected in milk from Vietnamese people living in Agent Orange-sprayed areas where consumption of fish was high. Furthermore, also in the 1970s, elevated TCDD levels (up to 810 ppt) were found in fish and shrimp from the same area as the milk donors. In the 1980s, we found elevated TCDD and also other organohalogen levels in human tissue, pork, fish, a turtle, and a snake in Southern Vietnam. For these reasons, we recently collected food from Bien Hoa and analyzed it for dioxins, polychlorinated biphenyls (PCBs), DDT and its metabolites, and other organochlorines. We found marked elevation of TCDD, the dioxin characteristic of Agent Orange, in some of the food products, including ducks with 276 ppt and 331 ppt wet weight, chickens from 0.031-15 ppt wet weight, fish from 0.063-65 ppt wet weight, and a toad with 56 ppt wet weight. Usual TCDD levels in food are less than 0.1 ppt. Total TEQ for ducks was from 286-343 ppt wet weight or 536 ppt and 550 ppt lipid; for chickens from 0.35-48 ppt wet weight or 0.95-74 ppt lipid, for fish from 0.19-66 ppt wet weight or 3.2 ppt and 15,349 ppt lipid, and the toad was 80 ppt wet weight and 11,765 ppt lipid. Interestingly, this study did not find elevated levels of TCDD in the pork and beef samples. Clearly, food, including duck, chicken, some fish, and a toad, appears responsible for elevated TCDD in residents of Bien Hoa City, even though the original Agent Orange contamination occurred 30-40 years before sampling. Elevated levels of PCBs and DDT and its metabolites were found in some food samples. Furthermore, measurable levels of hexachlorocyclohexanes (HCH) and hexachlorobenzene (HCB) were found in a wide range of measurable levels. All of the 11 dioxin-like PCBs measured and presented plus 6 dioxins in addition to TCDD and 10 dibenzofurans contributed to the total dioxin toxicity (TEQ). However, when elevated, TCDD frequently contributed most of the TEQ. Thirty-six congeners from 7 classes of chemicals were measured in each of the 16 specimens providing a total of 576 congener levels.     

Possible risk of endometriosis for Seveso, Italy, residents: an assessment of exposure to dioxin.

A recent study by Rier et al. showed that rhesus monkeys exposed daily for 4 years to 5 or 25 ppt of dioxin in food develop endometriosis, with incidence and severity related to dose. We aimed to determine whether the total time-integrated dioxin exposure of a human population could be comparable to that of Rier's monkeys. We selected a sample of residents of Seveso, Italy, who were acutely exposed to high levels of dioxin following an accident in 1976. We conducted a toxicokinetic analysis which takes into account species and exposure differences in dose and timing between humans and monkeys. The area under the time-concentration curve for dioxin in fat, which corresponds to cumulative exposure over time, ranges for some of the most heavily exposed Seveso residents from approximately 1.7 x 10(6) ppt-days to 1.1 x 10(8) ppt-days. These values exceed in all cases the values for the monkeys exposed to 25 ppt or 5 ppt. Given their exposure, the Seveso population should be an ideal epidemiologic cohort to rule out or confirm whether exposure to dioxin leads to an increased risk of endometriosis in humans.     

Relationship between emotional stress in female residents of the city of Chapaevsk and toxicological and genetic values

The severity of stress was evaluated in 45 female residents of the town of Chapaevsk (3 groups, 14-15 females each, with different levels of exposure to dioxins) using 5 standard psychological questionnaires. The results of testing were correlated to plasma dioxin concentrations and levels of chromosome aberrations in peripheral blood lymphocytes of the same donors. The results indicate that the groups differed by the degree of stress, the highest level being observed in women occupationally exposed to dioxins. The severity of stress correlated with plasma dioxin concentrations (p < or = 0.001) and levels and spectra of chromosomal aberrations in peripheral blood cells (p < or = 0.05, p < or = 0.01 in different tests). Presumably, one of the causes of high level of chromosomal aberrations in these women is dioxin-induced decrease of the adaptation potential, resulting in increase of the genome sensitivity to genotoxic factors of other origin).     

Correlates of serum dioxin to self-reported exposure factors

The aim of the current analysis was to examine the determinates of lipid-adjusted body levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from occupational histories, age, body mass index, and self-reported information from a questionnaire. We collected serum from 346 workers at a New Zealand chemical plant that manufactured and formulated the herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Age, body mass index, and employment history were significant determinates of TCDD. The self-reported data on occupation, residence, and general diet were not predictive of serum levels and we observed no evidence of increased TCDD levels from living close to the site. For participants with putative occupational exposure, employment history and personal factors were important to understand the range of TCDD serum levels. For employees without direct occupational exposure, and resulting lower dioxin levels, we recommend further efforts to develop and validate questionnaires to better evaluate environmental sources of dioxins.     

Sexually dimorphic behavioral responses to prenatal dioxin exposure

Pregnant Sprague-Dawley rats received a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin on day 8 of gestation. Each litter contributed a single male-female pair trained to press a lever to obtain food pellets under two operant behavior procedures. Initially, each lever press was reinforced. The fixed-ratio (FR) requirement was then increased every four sessions from the initial setting of 1 to values between 6 and 71. We then studied responses for 30 days under a multiple schedule combining FR 11 and another schedule requiring a pause of at least 10 sec between responses (DRL 10-sec). TCDD evoked a sexually dimorphic response pattern. Generally, TCDD-exposed males responded at lower rates than control males. In contrast, exposed females responded at higher rates than controls. Each response measure from the mult-FR DRL schedule yielded a male-female difference score. We used the differences in response rate to calculate benchmark doses based on the relative displacement from modeled zero-dose performance of the effective dose at 1% (ED(01)) and 10% (ED(10)), as determined by a second-order polynomial fit to the dose-effect function. For the male-female difference in FR rate of responding, the mean ED(10) was 2.77 ng/kg with a 95% lower bound of 1.81 ng/kg. The corresponding ED(01) was 0.27 ng/kg with a 95% lower bound of 0.18 ng/kg. For the male-female difference in DRL rate, the mean ED(10) was 2.97 ng/kg with a 95% lower bound of 2.02 ng/kg. The corresponding ED(01) was 0.30 ng/kg with a 95% lower bound of 0.20 ng/kg. These values fall close to, but below, current estimates of human body burdens of 13 ng/kg, based on TCDD toxic equivalents.     

Recent dioxin contamination from Agent Orange in residents of a southern Vietnam city

Marked elevation of dioxin associated with the herbicide Agent Orange was recently found in 19 of 20 blood samples from persons living in Bien Hoa, a large city in southern Vietnam. This city is located near an air base that was used for Agent Orange spray missions between 1962 and 1970. A spill of Agent Orange occurred at this air base more than 30 years before blood samples were collected in 1999. Samples were collected, frozen, and sent to a World Health Organization--certified dioxin laboratory for congener-specific analysis as part of a Vietnam Red Cross project. Previous analyses of more than 2200 pooled blood samples collected in the 1990s identified Bien Hoa as one of several southern Vietnam areas with persons having elevated blood dioxin levels from exposure to Agent Orange. In sharp contrast to this study, our previous research showed decreasing tissue dioxin levels over time since 1970. Only the dioxin that contaminated Agent Orange, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was elevated in the blood of 19 of 20 persons sampled from Bien Hoa. A comparison, pooled sample from 100 residents of Hanoi, where Agent Orange was not used, measured blood TCDD levels of 2 parts per trillion (ppt). TCDD levels of up to 271 ppt, a 135-fold increase, were found in Bien Hoa residents. TCDD contamination was also found in some nearby soil and sediment samples. Persons new to this region and children born after Agent Orange spraying ended also had elevated TCDD levels. This TCDD uptake was recent and occurred decades after spraying ended. We hypothesize that a major route of current and past exposures is from the movement of dioxin from soil into river sediment, then into fish, and from fish consumption into people.     

Serum dioxin levels in residents of Calcasieu and Lafayette parishes, Louisiana with comparison to the US population

The Agency for Toxic Substances and Disease Registry (ATSDR) used a cross-sectional study to compare the serum dioxin toxic equivalent (TEQ) levels of a population-based representative sample of Calcasieu Parish residents aged 15 years and older to a similar group of residents of Lafayette Parish with less industrial facilities. Serum dioxins consisted of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls. Overall, the mean and distribution of serum dioxin TEQ level in residents of both parishes were similar by age groups (15-29 years, 30-44 years, 45-59 years, and 60 year and older). When the Calcasieu Parish area was further divided based on distance to three industrial areas, the mean dioxin TEQ levels were similar. Serum dioxin TEQ levels in residents of both parishes increased with age. Calcasieu Parish residents who reported having eaten locally caught fish, smoked cigarettes, worked in an occupation with potential exposure, or used pesticides had dioxin levels similar to Lafayette Parish residents who reported these activities. African Americans had higher dioxin levels than Caucasians in Lafayette Parish and both races in Calcasieu Parish. The congener profiles were similar in residents of both parishes. When the combined Calcasieu and Lafayette Parish data were compared by age group to the National Health and Nutrition Examination Survey (NHANES) 2001-2002 data, the geometric means for the dioxin levels in the combined Parish data set were significantly lower than the NHANES data in all age groups (all P-values <0.0001), except the oldest age group where the significance level is marginal (P=0.067). The various percentiles of the youngest age group of the combined parish data were also significantly lower than those in NHANES. Since the combined parish dioxin levels were below a representative sampling of the US population, there is no increase in serum dioxin concentrations in both the parishes.     

Mercury exposure among residents of a building block in Shiraz, Iran

Exposure to mercury can cause serious multiorgan damage affecting the central nervous system, kidneys, liver, lungs, spleen, bone marrow, and skin. At the end of the summer of 1999, the accidental leakage of 4 liters of mercury from a container into the waterway canals resulted in mass exposure to elemental mercury among the residents of a building block of a residential area of the city of Shiraz, in the south of Iran. One hundred and eleven individuals who experienced exposure to elemental mercury were investigated. Twenty-four-hour measurement of the urine mercury level-revealed a toxic level of more than 20 microg/L in 6 children and 3 adults (including a pregnant woman). Despite normal physical and laboratory (CBC, renal and liver function tests, and urinalysis) findings, dimercaprol was prescribed. One month later during the course of the follow-up the urine mercury level in 6 patients, including the pregnant woman from the same family, was found to be again at a toxic level. The pregnant mother from the same family aborted her fetus; however, due to the lack of equipment for measuring the serum mercury level, it was not possible to confirm the relation between the mercury toxicity and the abortion. This family had kept mercury in their kitchen against health workers' instructions. The attractive physical and chemical properties of mercury could explain the continuity of exposure and poisoning in these 6 cases. It is concluded that prophylactic therapy in the presence of toxic levels of mercury, despite the presence of an asymptomatic state in exposed residents, is effective in preventing the development of signs and symptoms, though instruction of high-risk cases is the best way to combat it.     

Sources of nitrate exposure in residents of rural areas in Quebec, Canada

Nitrate exposure was investigated in a group of 187 people using well water and living in four areas of rural Quebec (Canada) with intensive agricultural activities. Nitrate intake was evaluated using a 24-h dietary recall and a food frequency questionnaire, in conjunction with a validated food database and measurements of nitrate concentrations in private wells. The total internal dose was estimated by means of the 24-h urinary nitrate excretion, while taking into account risk factors for endogenous nitrate formation. Mean (geometric) 24-h urinary nitrate excretion was 16.9 mg N for the 100 people with low groundwater contamination (mean nitrate concentration=0.18 mg N/l) and 23.3 mg N in the 87 individuals with moderate groundwater contamination (mean nitrate concentration=7.1 mg N/l). A multivariate analysis revealed that dietary nitrate intake during the last 24 h was the principal source of exposure, followed by water intake during the last 24 h. The Quetelet index was also a significant predictor of urinary excretion. The total predictive model explained only 29% of the variability in urinary nitrate excretion (R2=0.286). Neither the inflammatory status as indicated by elevated C reactive protein, the presence of Helicobacter pylori antibodies nor the occurrence of diarrhea during the last 24 h prior to urine collection were associated with urinary nitrate excretion. In conclusion, food and to a lesser extent water contribute to nitrate exposure in this rural setting with moderate water contamination. Better predictors of endogenous nitrate production are needed to improve our ability to model nitrate body burden and estimate associated health risks.     

Significant issues raised by meta-analyses of cancer mortality and dioxin exposure

Consistent with results from an earlier U.S. Environmental Protection Agency meta-analysis of three occupational cohorts, Crump et al. [Environ Health Perspect 111:681-687 (2003)] recently concluded that "dioxin TEQ [toxic equivalent] exposures within roughly 3-fold of current background levels may be carcinogenic" to humans. In contrast, my meta-analysis using an intercept-only model implied zero additional human cancer deaths from all exposures to dioxin-like compounds, including those arising via dietary intake. How can different investigators reach such markedly different conclusions from similar analyses of essentially the same data? The answer lies in different selections for a dose metric, different assumptions regarding the elimination half-life for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans, different assumptions regarding the importance of the most recent 15 years of exposure, and extrapolations from potential effects of TCDD exposure to potential effects of TEQ exposures. Resolution of the ongoing debate regarding the potential human carcinogenicity of dioxin will require detailed information on exposure to TCDD and on direct-acting carcinogens in the workplace, as well as a dose-response model that adequately reflects TCDD''s characteristics as a promoter.     

贵州某环境污染区人群镉暴露水平分析

目的了解贵州某镉污染区农作物污染状况及人群镉暴露水平。方法通过随机抽样方法获得调查人群(1 349人),采用三日询问法获得人群膳食消费量,原子吸收法测定膳食镉含量,电感耦合等离子质谱检测尿镉用于内暴露评估。结果采集粮食样品957份。完成186人的膳食调查和1 349人尿样筛查。污染区玉米、土豆及青菜的镉含量超过食物中镉限量值,青菜镉含量(均值0.2 mg/kg)高于其他食物,青菜镉的贡献达50.8%。污染区90%以上人群膳食镉暴露超标,90%以上人群尿镉超过2μg/g·Cr, 70%以上人群尿镉超过5μg/g·Cr, 10%左右人群尿镉超过15μg/g·Cr。结论膳食中镉主要来源为青菜,防止通过农作物—人食物链的人体镉暴露,建议定期开展健康筛查。     

贵州某环境污染区人群镉暴露水平分析

目的 了解贵州某镉污染区农作物污染状况及人群镉暴露水平.方法 通过随机抽样方法获得调查人群(1 349人),采用三日询问法获得人群膳食消费量,原子吸收法测定膳食镉含量,电感耦合等离子质谱检测尿镉用于内暴露评估.结果 采集粮食样品957份.完成186人的膳食调查和1 349人尿样筛查.污染区玉米、土豆及青菜的镉含量超过食...     

北京市某垃圾焚烧厂周边大气二噁英污染特征及暴露风险

  目的   基于北京某垃圾焚烧厂的二噁英排放数据,评估其周边居民通过不同暴露途径面临的健康风险。  方法   参考美国加州热点计划,采用AERMOD模型,模拟北京某垃圾焚烧厂排放二噁英在大气中的扩散情况;借助多介质扩散模型,模拟二噁英在不同环境介质中的扩散情况;计算垃圾焚烧厂周边居民通过不同暴露途径的二噁英摄入量,评估人群终身致癌风险。  结果   在垃圾焚烧厂周边最大落地点浓度处,居民通过呼吸、皮肤接触、泥土摄入和母乳喂养等途径面临的终身致癌风险为5.28 × 10^–7;当居民饮用水来自于5大水库,饮食取自垃圾焚烧厂周边蔬菜基地、养殖场和水库时,所面临的终身致癌风险为1.77 × 10^–8。  结论   该垃圾焚烧厂在现有排放状况下,其周边居民面临的健康风险在充分安全边际内,其中呼吸和母乳喂养是最主要的暴露途径。     

Health effects of dioxin exposure: a 20-year mortality study

Follow-up of the population exposed to dioxin after the 1976 accident in Seveso, Italy, was extended to 1996. During the entire observation period, all-cause and all-cancer mortality did not increase. Fifteen years after the accident, mortality among men in high-exposure zones A (804 inhabitants) and B (5,941 inhabitants) increased from all cancers (rate ratio (RR) = 1.3, 95% confidence interval (CI): 1.0, 1.7), rectal cancer (RR = 2.4, 95% CI: 1.2, 4.6), and lung cancer (RR = 1.3, 95% CI: 1.0, 1.7), with no latency-related pattern for rectal or lung cancer. An excess of lymphohemopoietic neoplasms was found in both genders (RR = 1.7, 95% CI: 1.2, 2.5). Hodgkin's disease risk was elevated in the first 10-year observation period (RR = 4.9, 95% CI: 1.5, 16.4), whereas the highest increase for non-Hodgkin's lymphoma (RR = 2.8, 95% CI: 1.1, 7.0) and myeloid leukemia (RR = 3.8, 95% CI: 1.2, 12.5) occurred after 15 years. No soft tissue sarcoma cases were found in these zones (0.8 expected). An overall increase in diabetes was reported, notably among women (RR = 2.4, 95% CI: 1.2, 4.6). Chronic circulatory and respiratory diseases were moderately increased, suggesting a link with accident-related stressors and chemical exposure. Results support evaluation of dioxin as carcinogenic to humans and corroborate the hypotheses of its association with other health outcomes, including cardiovascular- and endocrine-related effects.     

Evaluation of serum dioxin congeners among residents near continuously burning municipal solid waste incinerators in Korea

The objective of this study was to evaluate the congeners of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in Korean serum samples as biological markers. Serum samples from 103 participants were analyzed. Participants consisted of 28 workers in municipal solid waste incinerators (MSWIs), and 21 men and 54 women who had lived for at least 3 years prior to 2002 in areas within 300 m of incinerators in large Korean cities. Serum samples were analyzed for 17 PCDD/PCDFs congeners by high resolution gas chromatography-high resolution mass spectrometry. Geometric mean (GM) PCDD/PCDF levels in the serum samples were 3.14, 8.04, 6.12 and 6.60 pg TEQ/g lipid for workers, male residents, female residents and the sum of male and female residents, respectively. The GM PCDD/PCDF level in the serum of workers was not significantly different from the values for residents near MSWIs. In the 75 participants who resided near MSWIs, the congeners that most contributed to the total TEQ were 1,2,3,6,7,8-hexachlorodibenzofuran (1,6-HxCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 1,2,3,4,6,7,8-heptachlorodibenzofuran (1,4,6-HpCDF), 1,2,3,7,8,9-hexachlorodibenzofuran (1,9-HxCDF), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (1,4-HxCDD), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (1,6-HxCDD). In the workers, the congeners that made the greatest contribution were 1,6-HxCDD, 4-PeCDF, 1,2,3,4,6,7,8-heptachlorodibenzop-dioxin (HpCDD), and 1,6-HxCDF. In conclusion, the serum TEQ levels for PCDD/PCDFs in the incinerator workers and residents near the MSWIs in Korea were lower than those reported for other countries. Comparison of the PCDD/PCDF levels of workers at MSWIs and nearby residents revealed no significant enhancement of PCDD/PCDF exposure in workers. PCDD/PCDF intake from animal origin was assumed to be lower than that of Europeans. Further studies of Korean foods are needed to clarify the exposure route for PCDD/PCDFs in the Korean population.