Non-exposed Reference Research Articles

Arsenic in water, food and cigarettes: A cancer risk to Pakistani population

Inorganic arsenic (iAs) in drinking water and food items has been associated with lung and bladder cancers in several countries including Pakistan. In present study water, food items were collected from Arsenic (As) endemic areas (southern part of Pakistan) during 2008–2012, to evaluate its impact on the health of local population. Exposure of As was checked by analyzing biological samples (blood and scalp hairs) of male lung and bladder cancer patients (smokers and non-smokers). For comparative purpose the healthy subjects of same age group and residential area as exposed referents (EXR) and from non-contaminated area (Hyderabad, Pakistan) as non-exposed referents (NER) were also selected. As concentration in drinking water, food and biological samples were analyzed using electrothermal atomic absorption spectrometry. The validation of technique was done by the analysis of certified reference material (CRM) of blood and hair samples. The As contents in drinking water and food were found 3–15-folds elevated than permissible limits, where as in biological samples; EXR have 2–3-folds higher than NER and cancer patients have 5–9-folds higher than NER. The significant difference was observed in smokers (P < 0.01). The outcomes of the study revealed that As levels were elevated in blood and scalp hair samples of both types of cancer subjects as compared to referents (P < 0.001). It was observed that the lung cancer patients (LCP) have 20–35% higher levels of As in both biological samples as compared to bladder cancer patients (BCP) due to smoking habit. This study has proved the correlation among As contaminated water, food and cigarette smoking between different types of cancer risks.

80 Cross-sectional study on respiratory symptoms in workers exposed to metalworking fluid aerosols

ObjectivesTo survey which respiratory symptoms are more prevalent in workers exposed to metalworking fluids (MWF) in machine shops compared with referents. Workers with common symptoms from the lower airways will...

Maternal smoking during pregnancy and reproductive health of daughters: a follow-up study spanning two decades

Does in utero exposure to constituents of cigarette smoke have a programming effect on daughters' age of menarche and markers of long-term reproductive health? In utero exposure to constituents of cigarette smoke was associated with earlier age of menarche and--to a lesser extent--changes in the testosterone profile of the young women. Studies observe potential effects of in utero exposure to constituents of cigarette smoke on the intrauterine formation of female gonads, but the consequences on long-term reproductive health in daughters remain unclear. A prospective cohort study was designed using data from 965 pregnant women enrolled prior to a routine 30th-week antenatal examination at a midwifery practice in Denmark from 1988 to 1989 and a follow-up of their 19-21-year-old daughters in 2008. The pregnant women provided information on lifestyle factors during pregnancy, including the exact number of cigarettes smoked per day during the first and the second trimesters. A total of 438 eligible daughters were asked to complete a web-based questionnaire on reproductive health and subsequently invited to participate in a clinical examination during 2008. Of the 367 daughters (84%) who answered the questionnaire, 267 (61%) agreed to further examination. Information on menstrual pattern was provided at examination, blood samples were drawn to be analyzed for serum levels of reproductive hormones [FSH, LH, estradiol (E(2)), sex hormone-binding globulin, anti-Müllerian hormone, dehydroepiandrosterone-sulphate (DHEAS), free testosterone and free E(2)] and number of follicles (2-9 mm) were examined by transvaginal ultrasound. The daughters were divided into three exposure groups according to the level of maternal smoking during first trimester [non-exposed (reference), low-exposed (mother smoking >0-9 cigarettes/day) and high-exposed (mother smoking ≥ 10 cigarettes/day)]. Data were analyzed by multiple regression analyses in which we adjusted for potential confounders. Both crude and adjusted test for trend were carried out using maternal smoking during the first trimester as a continuous variable. We observed an inverse association between in utero exposure to constituents of cigarette smoke and age of menarche (P = 0.001). Daughters exposed to >0-9 cigarettes/day debuted with -2.7 [95% confidence interval (CI) -5.2 to -0.1] percentage earlier age of menarche, whereas daughters exposed to ≥ 10 cigarettes/day had -4.1 (95% CI: -6.6 to -1.5) percentage earlier age of menarche corresponding to 6.5 (95% CI: -10.7 to -2.2) months. There was a non-significant tendency towards lower levels of testosterone and DHEAS with increasing in utero exposure to constituents of cigarette smoke but no associations with follicle number, cycle length or serum levels of the other reproductive hormones were observed. We collected information on age of menarche retrospectively but the recall time was relatively short (2-10 years) and the reported values were within the normal range of Caucasians. Analyses of reproductive hormones are presented only for the group of daughters who were non-users of hormonal contraceptives because users were excluded, leaving only a low number of daughters available for the analyses (n = 75), as reflected in the wide CIs. The analyses of hormones were further adjusted for menstrual phase at time of clinical examination (follicular, ovulation and luteal phase) because blood samples were not collected on a specific day of the menstrual cycle. This study supports the limited evidence of an inverse association between maternal smoking during pregnancy and age of menarche and further addresses to what extent reproductive capacity and hormones may be programmed by maternal smoking during pregnancy. A trend toward earlier maturation of females is suggested to have implications on long-term reproductive function. Supported by a scholarship from The Lundbeck Foundation (R93-A8476). No conflict of interest declared.

Impact of copper on the abundance and diversity of sulfate-reducing prokaryotes in two chilean marine sediments

We studied the abundance and diversity of the sulfate-reducing prokaryotes (SRPs) in two 30-cm marine chilean sediment cores, one with a long-term exposure to copper-mining residues, the other being a non-exposed reference sediment. The abundance of SRPs was quantified by qPCR of the dissimilatory sulfite reductase gene β-subunit (dsrB) and showed that SRPs are sensitive to high copper concentrations, as the mean number of SRPs all along the contaminated sediment was two orders of magnitude lower than in the reference sediment. SRP diversity was analyzed by using the dsrB-sequences-based PCR-DGGE method and constructing gene libraries for dsrB-sequences. Surprisingly, the diversity was comparable in both sediments, with dsrB sequences belonging to Desulfobacteraceae, Syntrophobacteraceae, and Desulfobulbaceae, SRP families previously described in marine sediments, and to a deep branching dsrAB lineage. The hypothesis of the presence of horizontal transfer of copper resistance genes in the microbial population of the polluted sediment is discussed.

Research capacity development in South African manganese mines to bridge exposure and neuropathologic outcomes

Manganese (Mn) is a common occupational exposure worldwide. Recent studies indicate clinical and imaging evidence of neurotoxicity in chronically exposed workers. The pathologic significance of these findings is unclear. South Africa produces over 80% of the world's Mn from mines from a desert region in the Northern Cape Province. An autopsy program at the National Institute for Occupational Health (NIOH) in South Africa has provided compensation to families for mining-related lung diseases for almost 100 years. Building on this, we implemented a brain autopsy program to investigate the feasibility of obtaining brains from South African Mn miners and non-exposed reference miners to investigate neuropathologic consequences of chronic Mn exposure. Employing an experienced occupational health nurse, we identified deceased miners within 100 square km of the Mn mines. The nurse was notified of any Mn (case) or other (reference) miner or ex-miner death by local medical practitioners, occupational health and mine physicians, and community members, and families were approached for consent to remove the brains in addition to the cardio-respiratory organs. Families of deceased miners who had an autopsy at the NIOH in Johannesburg were also approached. To confirm exposure in Mn miners, mean pallidal indices were compared between Mn miners and non-exposed reference miners. Sixty-eight potential brain donors were identified; we obtained consent from the families to remove 51 (75%). The mean autopsy interval was seven days. With optimized fixation methods, the tissue quality of the brains for gross and regular microscopic examination was excellent. Ex vivo MRI demonstrated increased pallidal index in Mn miners compared to reference miners. We conclude that obtaining brain tissue from deceased miners in South Africa is highly successful with only a modest investment in local infrastructure. Tissue quality was excellent and should be ideal to investigate the neuropathologic consequences of chronic occupational Mn exposure.

DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect

To study the associations between exposure to vapours and aerosols of bitumen and genotoxic effects, a cross-sectional and cross-shift study was conducted in 320 exposed workers and 118 non-exposed construction workers. Ambient air measurements were carried out to assess external exposure to vapours and aerosols of bitumen. Hydroxylated metabolites of naphthalene, phenanthrene and pyrene were measured in urine, whereas (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide ((+)-anti-BPDE), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodGuo) and DNA strand breaks were determined in blood. Significantly higher levels of 8-oxodGuo adducts and DNA strand breaks were found in both pre- and post-shift blood samples of exposed workers compared to those of the referents. No differences between exposed workers and referents were observed for (+)-anti-BPDE. Moreover, no positive associations between DNA damage and magnitude of airborne exposure to vapours and aerosols of bitumen could be observed in our study. Additionally, no relevant association between the urinary metabolites of PAH and the DNA damage in blood was observed. Overall, our results indicate increased oxidative DNA damage in workers exposed to vapours and aerosols of bitumen compared to non-exposed referents at the group level. However, increased DNA strand breaks in bitumen workers were still within the range of those found in non-exposed and healthy persons as reported earlier. Due to the lack of an association between oxidative DNA damage and exposure levels at the workplaces under study, the observed increase in genotoxic effects in bitumen workers cannot be attributed to vapours and aerosols of bitumen.

Epidemiology of Respiratory Symptoms and Changes in Biological Parameters Over 5 Years in Japanese Workers Engaged in Toner Manufacturing

PP-30-207 Background/Aims: After some cases of siderosilicosis caused by toner were reported in the Lancet in 1994, some further studies reported granulomatous pneumonitis due to toner. However, few epidemiological studies discussing the effects of toner exposure on human health have been reported. This study aims to examine the relationship between work that involves exposure to printer/copying machine toner and development of respiratory disorders. Methods: A total of 1504 male workers between 19 and 50 years were selected from workers engaged in production of supplying materials, including toner in Japan. Subjects were divided into 2 groups: 768 subjects with exposure to toner via toner manufacturing and development, machine development, production and maintenance, and recycle process; and 736 nonexposed referents. In addition to annual health check, toner exposed state, respiratory symptoms, and various biological parameters such as pulmonary function and biochemical markers were examined. This report describes the annual results of a cross-sectional analysis and longitudinal survey for first 5 years. Results: Cross-sectional analysis showed significantly higher prevalence of respiratory symptoms in toner-exposed workers than nonexposed workers. In the longitudinal study, regarding the prevalence rate of most respiratory symptoms, especially acute or mild symptoms, difference between the 2 groups reduced year-on-year and the number of items that showed significant difference declined. Pulmonary function, blood cells, and biochemical markers did not consistently prove that tendency depends on toner exposure over the first 5 years. Conclusion: In this study conducted over 5 years, it became clear that exposure to toner did not result in clear harmful effects, but harmful effects caused by smoking on respiratory function, blood cells, and biochemical markers were much stronger. However, since difference in prevalence of respiratory symptoms might be due to information bias, to truly shed light on the effects of toner-exposure, it is important to continue the current 10-year cohort study.

Reference values and Z-scores for subregional femorotibial cartilage thickness – results from a large population-based sample (Framingham) and comparison with the non-exposed Osteoarthritis Initiative reference cohort

To establish sex-specific (subregional) reference values of cartilage thickness and potential maximal Z-scores in the femorotibial joint. The mean cartilage thickness (ThCtAB.Me) in femorotibial compartments, plates and subregions was determined on coronal magnetic resonance imaging (MRI) from a population-based sample (Framingham) and from a healthy reference sample of the Osteoarthritis Initiative (OAI). 686 Framingham participants (309 men, 377 women, age 62 ± 8 years) had no radiographic femorotibial osteoarthritis (OA) ("normals") and 376 (156 men, 220 women) additionally had no MRI features of cartilage lesions ("supernormals"). The Framingham "normals" had thinner cartilage in the medial (3.59 mm) than in the lateral femorotibial compartment (3.86 mm). Medially, the femur displayed thicker cartilage (1.86 mm) than the tibia (1.73 mm), and laterally the tibia thicker cartilage (2.09 mm) than the femur (1.77 mm). The thickest cartilage was observed in central, and the thinnest in external femorotibial subregions. Potential maximal Z-scores ranged from 5.6 to 9.8 throughout the subregions; men displayed thicker cartilage but similar potential maximal Z-scores as women. Mean values and potential maximal Z-scores in Framingham "supernormals" and non-exposed OAI reference participants (112 participants without symptoms or risk factors of knee OA) were similar to Framingham "normals". We provide reference values and potential maximal Z-scores of cartilage thickness in middle aged to elderly non-diseased populations without radiographic OA. Results were similar for "supernormal" participants without MRI features of cartilage lesions, and in a cohort without OA symptoms or risk factors. A cartilage thickness loss of around 27% is required for attaining a Z-score of -2.

Hallmarks of Posttraumatic Stress: Symptom Z-Scores in a Tsunami-Affected Tourist Population

Background: To date, little research has been published on the prominence of the various psychiatric symptoms that result from exposure to a natural disaster. In our study of stress-related symptoms among Norwegian tourists who were repatriated after the 2004 southeast Asian tsunami, we evaluated to what extent symptom scores differed between individuals who were exposed to the disaster and those who were not. Methods: Participants (n = 899) completed a questionnaire via post 6 months after the disaster. The participants were categorized according to their level of exposure to the disaster: danger exposed (caught or chased by the waves), nondanger exposed (other disaster-related stressors) and not exposed. Symptoms were assessed by the General Health Questionnaire (GHQ-28), the Post Traumatic Symptom Scale (PTSS-10), and the Impact of Event Scale – Revised (IES-R). We used z-transformation of symptom scores (Z-scores) to evaluate the extent to which symptom scores among disaster-exposed individuals differed from those in the nonexposed reference group. Results: The IES-R revealed the greatest differences between nonexposed and disaster-exposed individuals. Hyperarousal was the most prominent symptom cluster that related to disaster exposure, followed by intrusion and then avoidance. Symptoms of anxiety, social dysfunction, withdrawal, somatization and feelings of guilt were more closely linked to exposure than were symptoms of depression. Conclusions: Our results indicate that symptoms of hyperarousal may be more closely linked to acute exposure to a natural disaster such as a tsunami than other symptoms of psychological distress.

Neurotoxic effect of occupational exposure to mixed organic solvents in Korea: Posturographic study

This study used static posturography to investigate the neurotoxic effects on workers exposed to mixed organic solvents at low concentrations under the levels of the threshold limit values (TLV). Forty-one workers from four plants exposed to mixed solvents and 90 non-exposed referents were examined. The lifetime cumulative biological exposure (CE) was estimated according to subject's occupational history and biological monitoring results. Static posturography and questionnaire were the basis of data collection. The mean exposure index of mixed organic solvents of four plants was 0.47 (SD: 0.33, range: 0.08-1.39). The exposed group showed a larger sway area and length under the eye open condition than did the non-exposed group. In a multiple linear regression, a significant positive association was demonstrated between postural sway area and CE. This study results suggest that the exposure to organic solvents under TLV levels may cause disturbance in postural stability.

HOGG1326, XRCC1399 and XRCC3241 polymorphisms influence micronucleus frequencies in human lymphocytes in vivo

A pooled analysis of five biomonitoring studies was performed to assess the influence of hOGG1(326), XRCC1(399) and XRCC3(241) gene polymorphisms on micronuclei (MN) frequency in human peripheral blood lymphocytes, as measured by the ex vivo/in vitro cytokinesis-block micronucleus (CBMN) assay. Each study addressed a type of occupational exposure potentially able to induce DNA strand breakage (styrene, ionising radiation, cobalt/hard metal, welding fumes and inorganic arsenite compounds), and therefore MN, as a result of base excision repair and double-strand break repair deficiencies. The effect of genotype, age, exposure to genotoxic agents and smoking habit on MN induction was determined using Poisson regression analysis in 171 occupationally exposed male workers and in 132 non-exposed male referents. The analysis of genotype-genotype, genotype-smoking and genotype-exposure interactions by linear combinations of parameters showed significantly higher MN frequencies in the following subsets: (i) occupationally exposed workers carrying either the Thr/Thr or the Thr/Met XRCC3(241) genotypes compared to their referent counterparts (P < 0.001) and (ii) carriers of the Met/Met XRCC3(241) genotype compared to Thr/Thr XRCC3(241) carriers, as far as they are non-exposed and bear the variant (Ser/Cys or Cys/Cys) hOGG1(326) genotype (P < 0.01). Significantly lower MN frequencies were observed in carriers of the variant hOGG1(326) genotype compared to Ser/Ser hOGG1(326) carriers in the subgroup of non-smokers with Thr/Thr XRCC3(241) genotype (P < 0.01). Stratified analysis by occupational exposure showed a significant MN increase with smoking in occupationally exposed carriers of the Arg/Gln XRCC1(399)genotype (P < 0.001). In contrast, a significant MN decrease with smoking was observed in referents carrying the Ser/Ser hOGG1(326) genotype (P < 0.01). These findings provide evidence that the combination of different DNA repair genes and their interaction with environmental genotoxic agents may modulate MN induction. Understanding the complexity of the relationships between exposure, DNA repair and MN frequencies require larger scale studies and complementary biomarkers.

Time-to-pregnancy among male greenhouse workers

Objectives: Fertility problems are an increasing public health issue in industrialised countries. Exposure to exogenous agents with endocrine disrupting properties, such as some pesticides, are potential risk factors for subfertility....

Paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and birth outcomes of offspring: birth weight, preterm delivery, and birth defects.

Agent Orange is a phenoxy herbicide that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We studied pregnancy outcomes among wives of male chemical workers who were highly exposed to chemicals contaminated with TCDD and among wives of nonexposed neighborhood referents. For exposed pregnancies, we estimated serum TCDD concentration at the time of conception using a pharmacokinetic model. The mean TCDD concentration for workers’ births was 254 pg/g lipid (range, 3–16,340 pg/g). The mean referent concentration of 6 pg/g was assigned to pregnancies fathered by workers before exposure. A total of 1,117 live singleton births of 217 referent wives and 176 worker wives were included. Only full-term births were included in the birth weight analysis (≥37 weeks of gestation). Mean birth weight among full-term babies was similar among referents’ babies (n = 604), preexposure workers’ babies (n = 221), and exposed workers’ babies (n = 292) (3,420, 3,347, and 3,442 g, respectively). Neither continuous nor categorical TCDD concentration had an effect on birth weight for term infants after adjustment for infant sex, mother’s education, parity, prenatal cigarette smoking, and gestation length. An analysis to estimate potential direct exposure of the wives during periods of workers’ exposure yielded a nonstatistically significant increase in infant birth weight of 130 g in the highest exposure group (TCDD concentration > 254 pg/g) compared with referents (p = 0.09). Mothers’ reports of preterm delivery showed a somewhat protective association with paternal TCDD (log) concentration (odds ratio = 0.8; 95% confidence interval, 0.6–1.1). We also include descriptive information on reported birth defects. Because the estimated TCDD concentrations in this population were much higher than in other studies, the results indicate that TCDD is unlikely to increase the risk of low birth weight or preterm delivery through a paternal mechanism.

Cohort mortality study among French asphalt workers.

In conjunction with the European cohort study among asphalt workers coordinated by the International Agency for Research on Cancer (IARC), we studied the mortality of 15,011 French men who were followed for 17 years for a total of 175,062 persons-years. This group contained 2,506 subjects who had ever been employed as asphalt workers: they contributed 30,692 person-years of risk. A reference group was composed of 6,675 subjects (i.e., 61,856 persons-years) who had been employed only in building or ground construction. Mortality ratios standardized for age and period were computed with their 95% confidence intervals (CI) from the age and period mortality rates of all French men for the years covered by the study (1979-1996). We also compared the mortality of exposed workers and the reference group with Poisson regression models after adjustment for age, calendar period, and either duration of employment or length of follow-up. Mortality from lung cancer was equivalent to the expected rate [SMR = 1.01 95% CI (0.6-1.6)], but was 40% greater than among the non-exposed reference group [RR = 1.4 95% CI (0.7-2.8)]. We also found an excess of gastrointestinal cancers, especially of the esophagus [SMR = 1.94, 95% CI (0.9-3.6)] and stomach [SMR = 2.2, 95% CI (0.8-4.7)]. Comparison with the internal reference group confirmed these findings, especially for stomach cancer [RR = 2.8, 95% CI (0.7-11.4)]. Although our results are not statistically significant, they suggest that road-paving workers may have a slightly higher rate of lung cancer and a moderately higher rate of stomach cancer than their non-exposed counterparts. The excess of lung cancer may be due to potential confounding factors, including the occupational risk factor of coal tar exposure and the lifestyle risk factor of smoking. A nested case-control study is under way that will make it possible to control for smoking and other potential carcinogenic exposures; this is necessary before any definitive conclusions can be drawn.

Evaluation of the frequencies of chromosomal aberrations in a population exposed to prolonged low dose-rate 60 Co γ-irradiation

Purpose : Chromosomal aberration analysis in peripheral blood lymphocytes was performed to evaluate late cytogenetic effects of long-term low dose-rate γ-irradiation exposure among students and residents exposed in radiocontaminated buildings. Materials and methods : Blood samples were taken from 1913 subjects (age 17.8 ±13.6, mean ±SD) 5-8 years after their relocation from radioactive environments as well as from 176 non-exposed subjects (age 29.6 ±11.9) from the local community. Their lymphocytes were cultured for 48 h and metaphase spreads were prepared. A total of 208 900 metaphases were analysed for different types of chromosomal aberrations. Results : Relatively higher frequencies of translocations (2.1 ×10 -3) , rings (0.6 ×10 -3) and dicentrics (0.6 ×10 -3) were noted in the exposed population as compared with the nonexposed reference populations. Moreover, 356 (78.6%) of the 453 inversions were found on 14q11.2q32 in the exposed population. Among 392 well-demonstrated translocations, 167 (42.6%) and 175 (44.6%) occurred in chromosomes 7 and 14, respectively, while 139 (35.5%) occurred as t(7;14). In particular, the aberrations t(7;14)(p13;q11.2), t(7;14)(p15;q11.2) and t(7;14)(q36;q11.2) were the most prevalent, occurring with frequencies of 19 (13.7%), 20 (14.4%) and 27 (19.4%), respectively. In these, 3205 breakpoints were documented, with chromosomes 7, 9 and 14 shown to carry significantly higher frequencies of breakpoints than expected (≤2 -test, p <0.0001). A further six hotspots were identified on 7p15 (57, 1.8%), 7q36 (42, 1.3%), 9q12 (244, 7.6%), 9q13 (86, 2.7%), 14q11.2 (509, 15.9%) and 14q32 (387, 12.1%) in the exposed population. Conclusion : In comparison with the unexposed population, we observed increased frequencies of various chromosomal aberrations in this human population with previous exposure to prolonged low dose-rate γ-radiation. Moreover, several hotspot breakpoints and inversions and translocations were observed on chromosomes 7 and 14.

Spontaneous Abortion, Sex Ratio, and Paternal Occupational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

There is conflicting research regarding an association between fetal death and paternal exposure to Agent Orange, a phenoxy herbicide widely used in Vietnam that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Men who worked in the U.S. factories that produced Agent Orange were exposed to TCDD at levels hundreds of times higher than TCDD levels in the general population. Wives of TCDD-exposed chemical workers and wives of nonexposed neighborhood referents were interviewed to determine reproductive history. Paternal serum TCDD level at time of conception was estimated for each pregnancy using serum samples taken in 1987. Estimated TCDD levels of workers during or after exposure were high (median, 254 ppt; range, 3-16,340 ppt) compared to referent levels (median, 6 ppt; range, 2-19 ppt). No association between paternal TCDD level at the time of conception and spontaneous abortion was observed among pregnancies fathered by workers with TCDD levels of &lt; 20 ppt [odds ratio (OR) = 0.77; 95% confidence interval (CI), 0.48-1.22], 20 to &lt; 255 ppt (OR = 0.81; 95% CI, 0.40-1.63), 255 to &lt; 1,120, (OR = 0.69; 95% CI, 0.30-1.58), and &gt;or= 1,120 ppt (OR = 0.95; 95% CI, 0.42-2.17) compared to pregnancies fathered by referents. The sex ratio [males/(males + females)] of offspring also did not differ by TCDD exposure (0.53 and 0.54 among workers and referents, respectively). We did not find an association between paternal serum TCDD level and spontaneous abortion or sex ratio of offspring in this population. The estimated TCDD levels in this exposed worker population were much higher than in other studies, providing additional evidence that paternal TCDD exposure does not increase the risk of spontaneous abortion at levels above those observed in the general population. The study could not evaluate the effect of father's childhood or prenatal TCDD exposure on subsequent sex ratio.

Spontaneous abortion, sex ratio, and paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

There is conflicting research regarding an association between fetal death and paternal exposure to Agent Orange, a phenoxy herbicide widely used in Vietnam that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Men who worked in the U.S. factories that produced Agent Orange were exposed to TCDD at levels hundreds of times higher than TCDD levels in the general population. Wives of TCDD-exposed chemical workers and wives of nonexposed neighborhood referents were interviewed to determine reproductive history. Paternal serum TCDD level at time of conception was estimated for each pregnancy using serum samples taken in 1987. Estimated TCDD levels of workers during or after exposure were high (median, 254 ppt; range, 3-16,340 ppt) compared to referent levels (median, 6 ppt; range, 2-19 ppt). No association between paternal TCDD level at the time of conception and spontaneous abortion was observed among pregnancies fathered by workers with TCDD levels of < 20 ppt [odds ratio (OR) = 0.77; 95% confidence interval (CI), 0.48-1.22], 20 to < 255 ppt (OR = 0.81; 95% CI, 0.40-1.63), 255 to < 1,120, (OR = 0.69; 95% CI, 0.30-1.58), and >or= 1,120 ppt (OR = 0.95; 95% CI, 0.42-2.17) compared to pregnancies fathered by referents. The sex ratio [males/(males + females)] of offspring also did not differ by TCDD exposure (0.53 and 0.54 among workers and referents, respectively). We did not find an association between paternal serum TCDD level and spontaneous abortion or sex ratio of offspring in this population. The estimated TCDD levels in this exposed worker population were much higher than in other studies, providing additional evidence that paternal TCDD exposure does not increase the risk of spontaneous abortion at levels above those observed in the general population. The study could not evaluate the effect of father's childhood or prenatal TCDD exposure on subsequent sex ratio.

Comparison of representative ranges based on U.S. patient population and literature reference intervals for urinary trace elements

Reference intervals for trace elements are very hard to obtain because of the difficulty of defining a nonexposed reference population. However, representative ranges for trace elements obtained from a general patient population can provide useful information in interpreting laboratory results. We have used urine specimens submitted for trace metal analysis from patients residing in the United States to calculate representative ranges for 25 urinary trace elements, and to compare them to reference values taken from the literature. All urine analytes were measured by inductively-coupled plasma–mass spectrometry except chromium, which was measured by graphite furnace atomic absorption spectroscopy. For representative range calculation two approaches were used. In the non-parametric calculation first, the top 10% of results were discarded assuming that those specimens came from individuals with unusually high trace element exposures. Next the central 95% of the remaining data was taken as the reference interval. In the parametric calculation the specimens from exposed or not healthy individuals were assumed to appear as outliers and were discarded. The mean and S.D. were calculated, and used to determine representative ranges. The two approaches yielded very similar results, and worked remarkably well for 14 analytes. There were minor discrepancies for 7 analytes, and major for 4 analytes. All analyses of urinary trace elements included a urine creatinine value, which was used to express urinary trace element concentrations in terms of creatinine ratio. This corrects for differences in urine concentration that affects the results for random specimens.

Change in centromeric and acentromeric micronucleus frequencies in human populations after chronic radiation exposure.

Acute radiation exposure of humans was observed to induce various forms of cytogenetic damage, including increased frequencies of micronuclei and chromosomal aberrations. However, the cytogenetic effects of chronic low dose radiation exposure in vivo needs further characterization. Sixteen subjects with chronic low dose rates of gamma-radiation exposure from 60Co-contaminated steel in radioactive buildings were compared with seven non-exposed reference subjects for micronucleus frequencies after they relocated. By in situ hybridization using a digoxigenin-labeled anti-alpha all human centromere probe, the exposed subjects were shown to have a significant increase in cytochalasin B-modulated micronucleus (CBMN) frequencies, as well as a significant increase in centromere-positive (C+) CBMN, centromere-negative (C-) CBMN, total C+signals, single C+ MN signals and multiple C+ signals/1000 binucleated cells (BN). However, decreases in the ratios C+MN/C- MN and C+MN/total CBMN (%) were also noted in the exposed subjects. By mixed effects analysis, considering individuals from the same families, the C- MN and single C+ MN/1000 BN were both positively and moderately associated with previous cumulative exposure. When the time period of relocation post-exposure (relocation time or RT) was considered, total C+MN and multiple C+MN/1000 BN were negatively and significantly associated with RT. Moreover, the C+MN, C- MN, C+MN/C- MN ratio and single C+MN/1000 BN were all negatively and moderately associated with RT, but not with exposure dose. This suggested that acentromeric and single or multiple centromeric CBMN cytogenetic damage seems to disappear differentially in human subjects post chronic low dose radiation exposure.

Chronic low-dose gamma-radiation exposure and the alteration of the distribution of lymphocyte subpopulations in residents of radioactive buildings

Purpose : To elucidate the immunological change incurred in a human population by protracted gamma-radiation exposure at home environment. Materials and methods : An examination on the CD3+, CD4+, CD8+ and HLA-DR+ lymphocyte subsets was arranged for 196 exposed subjects with mean excess cumulative dose of 169mSv during 2-13 years of exposure. Another 55 close relatives of the exposed subjects were recruited as the non-exposed reference population. Results : The mean percentages of CD4+ T-lymphocytes, HLA-DR+ lymphocytes and the CD4+/CD8+ ratios in the exposed subjects (35.5, 19.9 and 1.51 respectively) were significantly lower than those of reference individuals (38.0, 22.6 and 1.72; p 0.02, 0.003, and 0.03 respectively), while the CD8 in total counts of the exposed was moderately increased above that of the reference populations (p=0.1). By ANOVA analysis, the percentages of CD4+ and HLA-DR+ subsets were significantly associated with radiation dose (p =0.0046, 0.003), while CD4+/CD8+ ratios were moderately associated with dose (p=0.073). HLA-DR+ counts were significantly and positively associated with duration of relocation from radioactive apartments (p=0.029). Conclusions : Significant immunological effects were observed in those who had received chronic low-dose radiation exposure.