Urinary mercury concentrations associated with dental restorations in adult women aged 16-49 years: United States, 1999-2000.

BACKGROUND: Mercury amalgam dental restorations have been used by dentists since the mid 19th century and issues on safety continue to be periodically debated within the scientific and public health communities. Previous studies have reported a positive association between urine mercury levels and the number of dental amalgams, but this relation has never been described in a nationally representative sample in the United States. AIMS AND METHODS: Using household interview, dietary interview, dental examination, and laboratory data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES), the association between mercury concentrations and dental restorations was examined in US women of reproductive age. RESULTS: In women of childbearing age, approximately 13% of all posterior dental surfaces were restored with amalgams and the average urinary mercury level in women was low (1.34 microg/l). It is estimated that an increase of 1.8 microg/l in the log transformed values for mercury in urine would occur for each 10 dental surfaces restored with amalgam. CONCLUSIONS: Although the findings do not address the important issues of adverse health effects at low thresholds of mercury exposure, they do provide important reference data that should contribute significantly to the ongoing scientific and public health policy debate on the use of dental amalgams in the USA.

The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina.

BACKGROUND: In a previous study, we did follow-up on 418 patients who were exposed to tryptophan in 1989, of whom 47 (11%) had definite and 63 (9%) possible eosinophilia-myalgia syndrome (EMS). METHODS: We assessed mortality and clinical spectrum of illness since 1989 for 242 (58%) of the 418 tryptophan-exposed patients from the original study. To assess outcomes, we used hospital and death records, interviewer-administered questionnaires, physical examinations, and laboratory tests. RESULTS: During the follow-up interval, mortality from all causes was 19% in those with definite EMS, 7% in possible EMS, and 3% in those who were not ill. The age- and sex-adjusted mortality in those with definite EMS was more than 3 times that of the general population or of tryptophan users in the practice who were not ill. Six deaths (66%) among the definite EMS case patients occurred during the 18 months immediately after symptom onset. Compared with the tryptophan users who were not ill, survivors with definite EMS continued to report excess morbidity for 6 major EMS symptoms (myalgia, arthralgia, weakness, rash, alopecia, and sclerodermiform skin changes), but they also reported that the symptom number and severity diminished with time. None of the tryptophan users who were not ill in 1989 developed a symptom complex suggesting new EMS during the follow-up interval. CONCLUSIONS: This study assessing a tryptophan-exposed population found those persons who developed EMS during the 1989 epidemic were at increased risk for death, particularly early after disease onset. Survivors reported improvement or resolution of major symptoms, suggesting that the severity of EMS diminishes with time. We found no evidence of delayed onset of EMS in tryptophan users who were not ill in 1989, regardless of the brand used.

Half-life of polybrominated biphenyl in human sera.

Polybrominated biphenyl (PBB), a flame-retardant material, was introduced into the food chain in Michigan in 1973 due to a manufacturing and distribution mistake. Following public concern about the long-term health effects of PBB in humans, a cohort of PBB-exposed Michigan residents was assembled in 1975. We initiated this study to determine the half-life of PBB in human sera and to understand how continued body burden relates to the possible adverse health consequences of PBB exposure. To determine the half-life, eligible persons were selected from the cohort if they had at least two PBB measurements 1 year apart and had an initial level > or = 20 pbb. There were 163 persons who met the criteria with a median PBB level of 45.5 ppb. The estimated half-life is 10.8 years (95% CI, 9.2-14.7 years). The body burden of PBB in exposed persons will decrease only gradually over time. For persons with an initial level of 45.5 ppb of PBB, it will take more than 60 years for their PBB levels to fall below the current level of detection of 1 ppb.

The U.S. federal framework for research on endocrine disruptors and an analysis of research programs supported during fiscal year 1996.

The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disruptor issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disruptors. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals; 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework. The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and polychlorinated biphenyls are the most commonly studied chemical classes. Comparison of the inventory with the research needs should allow identification of underrepresented research areas in need of attention.

Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

Changing sex ratio in the United States, 1969-1995.

OBJECTIVE: To determine if the sex ratio of live births in the United States has changed during the 27 years from 1969 through 1995. DESIGN: Regression analysis of secular trends in sex ratios. SETTING: Population-based data. PATIENT(S): Liveborn infants in the United States 1969-1995. MAIN OUTCOME MEASURE(S): Sex of liveborn infant. RESULT(S): The sex ratio (number of male births divided by number of female births) declined significantly among whites during the 27 years under study. Among black newborns, the sex ratio significantly increased during the same time period. CONCLUSION(S): These secular trends could not be explained by changing maternal or paternal age, or by changing proportions of specific birth orders. Possible explanations for the observed changes in sex ratio include random fluctuations in sex ratio over time, changes in demographic characteristics of the population (other than the characteristics controlled for in this analysis), and changes in frequency or timing of intercourse. Environmental exposures are unlikely to account for the observed trends.

Paternal occupation and Wilms' tumour in offspring.

A case-control study was conducted to test the hypothesis that paternal occupation is a risk factor for Wilms' tumour in offspring. Occupations associated with exposure to lead (Pb) and to hydrocarbons were examined by computing odds ratios, all of which were greater than unity but not by a statistically significant margin. When painters were considered separately, children whose fathers had been so employed were six times more likely to develop Wilms' tumour than children whose fathers had other occupations. Like the results for the Pb and hydrocarbon related occupations, the estimated relative risk associated with painters did not reach statistical significance. Although these data require cautious interpretation because of the relatively small number of subjects, the results reported here are not wholly consistent with the results of the one previous study of paternal occupation and Wilms' tumour in offspring.

Etiology of melanoma.

Although the precise etiology of melanoma remains unknown, much data link sunlight to melanoma. The imperfect evidence associating sun exposure (particularly UVB radiation) with melanoma emerges from human data, obviating problems inherent in extrapolation from animal and other models. However, the mechanism by which sunlight might possibly initiate or promote melanoma remains obscure. Some clarification should emerge from the potential isolation of genes that carry susceptibility to melanoma in families prone to the disease; such work could serve as a basis to distinguish genetic and environmental influences in melanoma [167]. Continued studies of faulty DNA repair in XP patients may elucidate the steps in mutagenesis and carcinogenesis. Future case-control studies must address the limits on the accuracy of recall and the limits on statistical methods to separate the cluster of phenotypic risk needed in determining biologically effective dose. Animal and in vitro studies must contribute more insight. Further research in the South American opossum models appears promising [72]. Although ozone depletion has been documented, there has been little definitive evidence of subsequent increase of UVB at the Earth's surface. Nevertheless, the threat posed by ozone depletion deserves continued environmental action and public education. The role of precursor lesions, particularly dysplastic nevi/atypical moles, must be clarified with future research. The distribution of melanoma among various work forces suggests that occupational risk factors may play an important role in the etiology of this disease [168-170]. The consistent reports of excess melanoma among accountants, clerical workers, professional workers, and teachers deserve further study. Furthermore, evidence of excesses in printing and press, petrochemical, and the telecommunications industries require follow-up. Carefully planned studies that account for nonoccupational risk factors are recommended. Research over the last four decades has brought much information about melanoma etiology. More work is needed to learn the precise cause and ultimately to prevent avoidable mortality from malignant melanoma.

Copper in drinking water, Nebraska, 1994.

In 1993, the levels of copper (Cu) in much of Nebraska's drinking water exceeded the U.S. Environmental Protection Agency's (EPA) action level of 1.3 mg/L. To determine the association of copper with gastrointestinal (GI) illness in August 1994 the authors interviewed persons living in households with 1993 Cu levels > 3 mg/L (51 households), 2-3 mg/L (54 households), and < 1.3 mg/L (43 households). Cases were defined as persons who had experienced the rapid onset of vomiting or nausea with abdominal pain during the preceding two weeks. To validate their exposure index, the authors immediately resampled drinking water in the households of 25 cases and 27 controls matched for age. Reassessment in December 1994 of the exposure and case status of the original cohort showed no association between copper in drinking water in 1993 and case status in 1994. The risk of GI illness seemed no greater with Cu > 3 mg/L (RR = 1.03; 95% CI = 0.43, 2.49) or 2-3 mg/L (RR = 0.50; 95% CI = 0.18, 1.41) than with Cu < 1.3 mg/L. The 1993 Cu concentrations could not be reproduced in August 1994; resampling in December 1994 again showed no association between GI illness and Cu exposure (RR > 1.3-2.9 mg/L, < or = 1.3 mg/L = 0.25, 95% CI = 0.10, 0.64, and RR > or = 3.0 mg/L, < or = 1.3 mg/L = 0.36, 95% CI = 0.09, 1.49).

Cardiovascular mortality--the hidden peril of heat waves.

OBJECTIVE: Define the mortality associated with extremely hot weather during the 04 July through 14 July, 1993 heat wave that struck the northeastern United States. METHODS: DESIGN--A rapid field assessment was used to compare mortality occurring during the heat wave to mortality occurring during a period in which there was no heat wave using copies of death certificates. The findings of the rapid field assessment were validated, and it was determined whether increases in mortality occurred in other metropolitan east-coast counties also affected by the heat wave, by reviewing computerized mortality files. SETTING--Information was collected on all deaths occurring in Baltimore City, Maryland; Baltimore County, Maryland; Essex County, New Jersey; Newcastle County, Delaware; and Philadelphia County, Pennsylvania; during these specified study periods: 08-18 June (comparison period) and 06-16 July (heat wave study period), 1993. MAIN OUTCOME MEASURES--Ratios for total mortality, cause-specific mortality, and variables such as age, sex, race, residence, and day and place of death, that were available from death certificates were calculated. RESULTS: From the rapid field assessment, the following were observed: a 26% increase in total mortality and a 98% increase in cardiovascular mortality associated with the heat wave in Philadelphia. Data from the computerized mortality files showed an increase in total mortality in four of five counties examined and an increase in cardiovascular mortality in all five counties. The risk for death for those dying from cardiovascular disease increased significantly for people older than 64 years, for both sexes, and all races. CONCLUSION: As initially indicated by the Philadelphia Medical Examiner, there was excess mortality associated with a heat wave in Philadelphia. All other nearby counties examined also experienced excess mortality associated with the heat wave, although this excess was not recognized by the local health officials. The true impact of a heat wave that causes excess preventable mortality must be appropriately and rapidly ascertained. Using a national standard to certify a death as heat-related will provide the needed information rapidly so that public health resources can be more effectively allocated and mobilized to prevent further heat-related illnesses and death.

Optimizing BeLPT criteria for beryllium sensitization.

BACKGROUND: The beryllium lymphocyte proliferation test (BeLPT) is used to identify persons sensitized to beryllium. ATSDR convened an expert panel of physicians and scientists in April 2006 to discuss this test and to consider what BeLPT test results actually establish beryllium sensitization. The three criteria proposed by panel members were (1)one abnormal result, (2)one abnormal and one borderline result, and (3)two abnormal results. METHODS: Complete algorithms were developed for each of the three proposed criteria. Using single-test outcome probabilities developed by Stange et al. [2004. Am J Ind Med 46:453-462], we calculated and compared the sensitivity, specificity, and positive predictive values (PPVs) for each set of criteria. RESULTS: The overall sensitivity and specificity of the three criteria were similar. When the criteria required confirmation of an abnormal result the PPV was higher--whether the requirement was satisfied by a borderline result, or only by another abnormal result. Confirmation also reduced the likelihood of false positives. The differences between the three criteria decreased as the prevalence of sensitization increased. CONCLUSIONS: A single unconfirmed abnormal is usually insufficient to establish sensitization for an apparently healthy person. When the prevalence of beryllium sensitization in a group is high, however, even a single abnormal BeLPT can be a strong predictor.

Parental occupation and intracranial neoplasms of childhood: results of a case-control interview study.

In 1983-1984, the authors conducted a case-control study of environmental factors and childhood brain tumor risk. Cases (n = 110) were identified through the tumor registry of a pediatric hospital and matched controls (n = 193) through random digit dialing. In addition to parental occupational histories, telephone interviews elicited information about potential confounders and hypothesized risk factors for childhood brain tumors. Relying primarily on the Hoar et al. (J Occup Med 1980;22:722-6) job-exposure matrix, the authors examined parental employment characteristics in relation to the relevant developmental periods. Paternal employment in several industries (agriculture, construction, metal, and food and tobacco) and in several occupations (agriculture, benchwork, and transportation) was associated with excess risk. The range of notably elevated odds ratios was 2.0-3.3, with all confidence intervals including 1.0 except one. Elevated but unstable odds ratios were also found for both paternal and maternal employment in jobs "clustered" together because of common exposures. For both approaches to exposure classification, the greatest excess risks were consistently demonstrated for parental jobs held in the preconception period. Job-exposure matrix analyses indicated that case fathers were more likely than control fathers to have had jobs linked with aromatic amino and aromatic nitro compounds (range of notably elevated (and unstable) odds ratios, 3.4-4.4), but here the greatest excess risks were exhibited in the postnatal period. Few associations emerged for maternal employment characteristics, although this is probably explained by the relatively small number of women employed in jobs outside the home.

Occupational exposures among fathers of children with Wilms' tumor.

An occupation-and-exposure linkage system was utilized to perform an epidemiologic case-control study of paternal occupation and Wilms' tumor in offspring. The first part of the study was designed to test the hypothesis that paternal lead (Pb) exposure is a risk factor for Wilms' tumor in offspring. The second part of the study was an exploratory analysis that sought to generate possible etiologic hypotheses about other paternal exposures in the workplace in relation to Wilms' tumor. Calculation of odds ratios indicated that there was no statistical difference in the frequency of occupational exposure to Pb, Pb alkyls, and Pb salts for fathers of children with Wilms' tumor and fathers of controls, a finding that contrasts sharply with the results of the one previously reported study in this area. In the exploratory phase of the study, case fathers were found more likely to have been exposed to boron, while control fathers were found more likely to have encountered insecticides, acetylene, o-chlorobenzylidene, oil orange ss, and diethylene glycol; the differences were statistically significant. Troublesome methodologic problems, including exposure misclassification, sample size, and multiple comparisons, are discussed.

Two episodes of acute illness in a machine shop.

Following an explosion in a machine shop and temporary plant closure, on the day the plant returned to full operations a degreaser malfunctioned. Workers in the assembly room were exposed to trichloroethylene levels later estimated to have exceeded 220 ppm (OSHA PEL 100 ppm). The plant was evacuated and the degreaser taken out of operation. Blood testing for carbon monoxide (CO) on five employees found carboxyhemoglobin levels in excess of normal. The plant reopened the following morning. Over the next two weeks, 15 employees were seen by the plant nurses for similar complaints; although all returned to work, their carboxyhemoglobin levels, later found to be inaccurate, were reported by a local medical clinic to range from 13.7 to 20.0 percent. At the end of the second week, another outbreak of illness occurred, but carboxyhemoglobin, trichloroethylene, fluorocarbons, and methylene chloride were not elevated in all 17 persons tested; plant-wide monitoring for CO found no elevated levels. During the first outbreak of illness, cases were 2.26 times as likely to have entered the assembly room as noncases. During the second outbreak, cases were no more likely than noncases to have entered the assembly room. We believe the explosion, earlier toxic exposures and illness, and the misleading blood test results led to plant-wide anxiety which culminated in a collective stress reaction and the second outbreak. An open meeting with all employees, informing them of our findings, provided reassurance and no further episodes of illness occurred in this workforce.

An outbreak of chromium ulcer in a manufacturing plant.

On May 23, 1989, managers of a manufacturing plant requested an investigation of an outbreak of hand ulceration and skin discoloration among workers. The plant has manufactured kitchen ranges for 30 years and employs approximately 633 hourly workers. The affected employees worked in the enamel department, where metallic range tops are coated with a "ground coat" or sprayed with an enamel coloring, and then baked in ovens at 1200F. Our evaluation included physical examinations, environmental sampling, and a questionnaire eliciting information concerning skin ulceration job history, demographics, and use of protective practices. We identified 10 enamel department workers (13.5%) who developed chromium ulcers between January 1st and June 30th, 1988. Ulcers were found on hands, forearms, periumbilical area and/or axillae. Within the enamel department, workers who handled conveyer hooks used to suspend range tops as they passed through the oven were at greatest risk (rate ratio (RR) = 12.44, 95% confidence interval (CI) = 2.90-53.35). Workers who wore gloves were protected from developing ulcers (RR = 0.08, 95% CI = 0.01-0.60). Normally, trivalent chromium (Cr+3) does not cause skin ulcers unless it is oxidized to hezavalent chromium Cr+6). The enamel used contained only Cr+3, not Cr+6, but analysis of hooks that had passed through the oven revealed Cr+6 on their surface. A mechanical failure of the oven resulted in the formation of sharp edges of the parts and consequently causing the abrasion of exposed skin. We believe Cr+3 was converted to Cr+6 during the baking process which associated with the mechanical failure of the oven causing this outbreak.

Mortality among workers exposed to polychlorinated biphenyls.

On the basis of evidence from animal studies, polychlorinated biphenyls (PCBs) are considered potentially carcinogenic to humans. However, the results of studies in human populations exposed to PCBs have been inconsistent. The authors conducted a retrospective cohort analysis (1957-1986) comparing the mortality of 3,588 electrical capacitor manufacturing workers with known exposure to PCBs with age-, sex-, and calendar time-specific mortality rates for all whites in the United States. Proportional hazards modeling was also performed to examine the association between cumulative PCB exposure and site-specific cancer mortality. All-cause mortality (192 deaths observed, 283.3 expected) and total cancer mortality (54 deaths observed, 63.7 expected) were lower than expected. More deaths were observed than expected for malignant melanoma (8 observed, less than 2.0 expected) and cancer of the brain and nervous system (5 observed, 2.8 expected). The average estimated cumulative dose for the cases of brain cancer (22.9 units) was greater than for other workers (12.9 units), but the 95% confidence intervals around this difference were broad. The risk of malignant melanoma was not related to cumulative PCB exposure. These results provide some evidence of an association between employment at this plant and malignant melanoma and cancer of the brain. The possibility that the results are due to chance, bias, or confounding cannot be excluded.

Parental occupation and intracranial neoplasms of childhood: anecdotal evidence from a unique occupational cancer cluster.

Near the end of the data-collection phase of a case-control interview study of environmental factors and childhood brain tumors, an unusual space-time cluster was revealed. Not only had six genetically unrelated children been diagnosed with a primary intracranial tumor in a recent 2.4 year period in a rural county in Ohio, but each child had one parent employed by the same company (two mothers, four fathers). This represents an observed/expected ratio greater than 70 (p much less than 0.001). All tumors were microscopically confirmed, and all case parents worked at the facility in question for at least 1 year prior to conception, during the index pregnancy, and for at least 6 months after birth. The place of parental employment was an electronics firm (Standard Industrial Classification [SIC] group number 367, electronic components and accessories), where more than 100 chemical compounds are used by the company in a manufacturing process. Results of the cluster investigation are described, including a description of the case series. This cancer cluster is unique in that the index case series is composed of the offspring of workers, not the workers themselves.

An epidemic of dermatitis at a large construction site.

During 6 months in 1986, an epidemic of dermatitis occurred among more than 5600 workers at a single large construction site in the United States. To identify its cause, we used the monthly nurses' log of visits to the medical facility to characterize the outbreak by person, place, and time. Follow-up studies included a survey of carpenters and skin testing of laboratory animals. Workers were more than twice as likely to visit the medical facility for a skin-related complaint in 1986 compared with 1985 (relative rate [RR] = 2.6, 95% confidence interval [CI] 2.2-3.2). Carpenters experienced the greatest increased risk (RR = 9.7, 95% CI 5.5-17.3). We found a strong association between dermatitis and handling of fire-retardant lumber and plywood. Carpenters working only with fire-retardant lumber had a rate of dermatitis 4 times that of carpenters who worked exclusively with untreated wood (RR = 3.6, 95% CI 1.5-8.6). Carpenters who occasionally worked with fire-retardant lumber and plywood were at moderate risk (RR = 2.18, 95% CI 0.7-6.7). Although laboratory tests showed that phosphate compounds could be leached with water from the fire-retardant wood, an extract of these phosphates did not irritate the skin of laboratory animals. We concluded the epidemic was a result of handling fire-retardant lumber but could not identify the specific chemical agent. In view of the observed association, construction workers should be advised to handle this material with caution, especially in high temperature and humidity.