John S. Reif

Geomagnetic disturbances are associated with reduced nocturnal excretion of a melatonin metabolite in humans

The effects of geomagnetic disturbances on urinary excretion of the melatonin metabolite, 6-hydroxymelatonin sulfate (6-OHMS), were studied in conjunction with 60 Hz magnetic field (MF) and ambient light exposure in 132 electric utility workers. Geomagnetic activity was assessed using a local (equivalent amplitude or A(K), Boulder, CO) and global (average antipodal or aa) index. Personal exposures to 60 Hz MFs and light were obtained using data-logging meters. The relationship between geomagnetic activity and 6-OHMS was assessed with adjustment for age, light exposure, and month of participation. Mean overnight 6-OHMS excretion was lower on days when the 36-h A(K) or aa values exceeded 30 nT. A greater reduction in 6-OHMS excretion was observed when increased geomagnetic activity was combined with elevated 60 Hz MF or reduced ambient light exposures.

Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs

A case-control study of household dogs was conducted to determine if exposure to sidestream cigarette smoke and chemicals in the home, use of topical insecticides, and obesity are associated with the occurrence of bladder cancer. Information was obtained by interview from owners of 59 dogs with transitional-cell carcinoma of the bladder and 71 age- and breed size-matched control dogs with other chronic diseases or neoplasms. Bladder cancer risk was unrelated to sidestream cigarette smoke and household chemical exposures. Risk was significantly increased by topical insecticide use (OR = 1.6 for 1-2 applications per year and OR = 3.5 for greater than 2 applications per year; chi 2 trend; p = .008). This risk was enhanced in overweight or obese dogs. Further studies of this canine model may facilitate identification of specific carcinogens present in insecticides commonly used on pet animals and in the environment.

Late Pregnancy Exposures to Disinfection By-products and Growth-Related Birth Outcomes

Toxicologic studies have demonstrated associations between growth-related birth outcomes and exposure to high concentrations of disinfection by-products (DBPs), including specific tri-halomethane (THM) and haloacetic acid (HAA) chemical subspecies. Few prior investigations of DBPs have evaluated exposure during the third trimester of pregnancy, the time period of gestation when fetal growth may be most sensitive to environmental influences. We conducted a retrospective cohort study to examine the effects of exposure to THMs and HAAs during the third trimester and during individual weeks and months of late gestation on the risks for term low birth weight, intrauterine growth retardation, and very preterm and preterm births. The study population (n = 48,119) included all live births and fetal deaths occurring from January 1998 through March 2003 to women whose residence was served by one of three community water treatment facilities. We found evidence of associations between exposure to specific HAAs and term low birth weight as well as intrauterine growth retardation and for exposure to the five regulated HAAs (HAA5) and term low birth weight. Our findings suggest a critical window of exposure with respect to fetal development during weeks 33–40 for the effects of dibromoacetic acid and during weeks 37–40 for the effects of dichloroacetic acid. Adjustment for potential confounders did not affect the conclusions.

RISK FACTORS FOR ADENOCARCINOMA OF THE LUNG

The relation between various risk factors and adenocarcinoma of the lung was evaluated in a case-control study. Subjects were selected from the Colorado Central Cancer Registry from 1979-1982 in the Denver metropolitan area. A total of 102 (50 males and 52 females) adenocarcinoma case interviews and 131 (65 males and 66 females) control interviews were completed. The control group consisted of persons with cancers of the colon and bone marrow. The risk estimates associated with cigarette smoking were significantly elevated among males (odds ratio (OR) = 4.49) and females (OR = 3.95) and were found to increase significantly (p less than 0.01) with increasing levels of cigarette smoking for both males and females. For adenocarcinoma in females, the age- and smoking-adjusted odds ratios at different levels of passive smoke exposure followed an increasing overall trend (p = 0.05). After additional adjustment for potential confounders, prior cigarette use remained the most significant predictor of risk of adenocarcinoma among males and females. Analysis restricted to nonsmoking females revealed a risk of adenocarcinoma of 1.68 (95% confidence interval (Cl) = 0.39-2.97) for passive smoke exposure of four or more hours per day. Neither sex showed significantly elevated risk for occupational exposures, although males bordered on significance (OR = 2.23, 95% Cl = 0.97-5.12). The results suggest the need to develop cell type-specific etiologic hypotheses.

Proximity to Natural Gas Wells and Reported Health Status: Results of a Household Survey in Washington County, Pennsylvania

Background: Little is known about the environmental and public health impact of unconventional natural gas extraction activities, including hydraulic fracturing, that occur near residential areas. Objectives: Our aim was to assess the relationship between household proximity to natural gas wells and reported health symptoms. Methods: We conducted a hypothesis-generating health symptom survey of 492 persons in 180 randomly selected households with ground-fed wells in an area of active natural gas drilling. Gas well proximity for each household was compared with the prevalence and frequency of reported dermal, respiratory, gastrointestinal, cardiovascular, and neurological symptoms. Results: The number of reported health symptoms per person was higher among residents living < 1 km (mean ± SD, 3.27 ± 3.72) compared with > 2 km from the nearest gas well (mean ± SD, 1.60 ± 2.14; p = 0.0002). In a model that adjusted for age, sex, household education, smoking, awareness of environmental risk, work type, and animals in house, reported skin conditions were more common in households < 1 km compared with > 2 km from the nearest gas well (odds ratio = 4.1; 95% CI: 1.4, 12.3; p = 0.01). Upper respiratory symptoms were also more frequently reported in persons living in households < 1 km from gas wells (39%) compared with households 1–2 km or > 2 km from the nearest well (31 and 18%, respectively) (p = 0.004). No equivalent correlation was found between well proximity and other reported groups of respiratory, neurological, cardiovascular, or gastrointestinal conditions. Conclusion: Although these results should be viewed as hypothesis generating, and the population studied was limited to households with a ground-fed water supply, proximity of natural gas wells may be associated with the prevalence of health symptoms including dermal and respiratory conditions in residents living near natural gas extraction activities. Further study of these associations, including the role of specific air and water exposures, is warranted. Citation: Rabinowitz PM, Slizovskiy IB, Lamers V, Trufan SJ, Holford TR, Dziura JD, Peduzzi PN, Kane MJ, Reif JS, Weiss TR, Stowe MH. 2015. Proximity to natural gas wells and reported health status: results of a household survey in Washington County, Pennsylvania. Environ Health Perspect 123:21–26; http://dx.doi.org/10.1289/ehp.1307732

An analysis of occupational risks for brain cancer.

We evaluated the risks of brain cancer in relation to employment history in a case-control study of 312 cases and 1,248 cancer controls. Subjects were identified through the Missouri Cancer Registry for the period 1984 through 1988. Job classification was based on data routinely abstracted from hospital records. Elevated risks were identified for certain white collar occupations: for men employed in engineering, the odds ratio (OR) = 2.1; 95% confidence interval (CI) = 0.4, 10.3; for social science professionals, the OR = 6.1; 95% CI = 1.5, 26.1. Among occupations with potential exposure to occupational carcinogens, increased risks were observed for men employed in agricultural crop production (OR = 1.5; 95% CI = 1.0, 2.4), printing and publishing (OR = 2.8; 95% CI = 1.0, 8.3), and brickmasons and tilesetters (OR = 2.5; 95% CI = 0.5, 11.5). Most of elevated brain cancer risks were due to astrocytic cancers, but the excess among agricultural workers occurred in other cell types. No increase in risk was noted for current cigarette smokers (OR = 0.9; 95% CI = 0.7, 1.5) or ex-smokers (OR = 1.0; 95% CI = 0.7, 1.5). This exploratory study indicates a need for further studies of occupational risks of brain cancer.

Melatonin metabolite excretion among cellular telephone users

Purpose : The relationship between cellular telephone use and excretion of the melatonin metabolite 6-hydroxymelatonin sulfate (6-OHMS) was evaluated in two populations of male electric utility workers (Study 1, n =149; Study 2, n =77). Materials and methods : Participants collected urine samples and recorded cellular telephone use over 3 consecutive workdays. Personal 60-Hz magnetic field (MF) and ambient light exposures were characterized on the same days using EMDEX II meters. A repeated measures analysis was used to assess the effects of cellular telephone use, alone and combined with MF exposures, after adjustment for age, participation month and light exposure. Results : No change in 6-OHMS excretion was observed among those with daily cellular telephone use >25 min in Study 1 (5 worker-days). Study 2 workers with >25 min cellular telephone use per day (13 worker-days) had lower creatinine-adjusted mean nocturnal 6-OHMS concentrations (p =0.05) and overnight 6-OHMS excretion (p =0.03) compared with those without cellular telephone use. There was also a linear trend of decreasing mean nocturnal 6-OHMS/creatinine concentrations (p =0.02) and overnight 6-OHMS excretion (p =0.08) across categories of increasing cellular telephone use. A combined effect of cellular telephone use and occupational 60-Hz MF exposure in reducing 6-OHMS excretion was also observed in Study 2. Conclusions : Exposure-related reductions in 6-OHMS excretion were observed in Study 2, where daily cellular telephone use of >25min was more prevalent. Prolonged use of cellular telephones may lead to reduced melatonin production, and elevated 60-Hz MF exposures may potentiate the effect.

Melatonin metabolite levels in workers exposed to 60-Hz magnetic fields : Work in substations and with 3-phase conductors

Melatonin suppression by 50/60-Hz magnetic fields represents a plausible biological mechanism for explaining increased health risks in workers. Personal exposure to magnetic fields and ambient light, and excretion of the melatonin metabolite 6-hydroxymelatonin sulfate (6-OHMS), were measured over 3 consecutive workdays in electric utility workers. There was a magnetic field-dependent reduction in adjusted mean nocturnal and post-work 6-OHMS levels among men working more than 2 hours per day in substation and 3-phase environments and no effect among those working 2 hours or less. No changes were observed among men working in 1-phase environments. The results suggest that circular or elliptical magnetic field polarization, or another factor linked to substations and 3-phase electricity, is associated with magnetic field induced melatonin suppression in humans.

Immune dysfunction in Atlantic bottlenose dolphins (Tursiops truncatus) with lobomycosis

Lobomycosis (Lacaziosis) occurs only in humans and dolphins under natural conditions. We evaluated the immune status of eight dolphins with lobomycosis and 40 healthy dolphins from the Indian River Lagoon (IRL), Florida. Lobomycosis cases had multiple abnormalities in their immunologic parameters when compared to healthy dolphins. The absolute number of circulating lymphocytes and serum albumin concentration were reduced (P<0.05) while the segmented neutrophils, alpha 1, total beta, total gamma and total globulins were increased (P<0.05). Although innate immunity was relatively intact and phagocytosis and natural killer cell activity were not affected, the plasma lysozyme concentrations were elevated in dolphins with lobomycosis (P<0.05). Adaptive immunity was depressed with statistically significant decreases found in the absolute numbers of CD4(+) helper T cells and CD19(+) and CD21(+) B cells. The ratios of CD2(+) T cells to CD4(+) cells and CD2(+) to CD21(+) cells were increased (P=0.05 and P<0.05, respectively) and the numbers of lymphocytes expressing MHC class II molecules was decreased in dolphins with lobomycosis (P<0.05). Lymphocyte proliferation was reduced in response to stimulation with lipopolysaccharide and concanavalin A (P<0.05). Antibody titers to Erysipelas rhusiopathiae, a common marine micro-organism, were decreased (P<0.05). In summary, dolphins with lobomycosis exhibit significant impairment in adaptive immunity.

Cancer risks among Missouri farmers

A series of case–control studies was conducted to investigate cancer risks among farmers. These studies were based on Missouri Cancer Registry data for 15,000 white male patients, including 1720 subjects classified as farmers, registered between 1984 and 1988. For each cancer site, all other cancer registrations formed the control group. The largest risks among farmers were found for lip cancer (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.99 to 4.73) and cancer of the bone (OR, 2.02; 95% CI, 0.66 to 5.81). Elevated risks were observed for several other sites, including the nasal cavity and sinuses (OR, 1.66; 95% CI, 0.54 to 4.70), prostate (OR, 1.33; 95% CI, 1.18 to 1.51), non‐Hodgkins lymphoma (OR, 1.40; 95% CI, 1.04 to 1.85), and multiple myeloma (OR, 1.40; 95% CI, 0.87 to 2.24). Other smaller elevations in risk were noticed for cancer of the rectum (OR, 1.21; 95% CI, 0.95 to 1.53), liver (OR, 1.19; 95% CI, 0.58 to 2.37), malignant melanoma (OR, 1.26; 95% CI, 0.63 to 2.45), kidney (OR, 1.21; 95% CI, 0.89 to 1.65), and leukemia (OR, 1.12; 95% CI, 0.81 to 1.55); however, some of these estimates were imprecise due to small numbers. The overall OR for lymphatic and hematopoietic cancers was 1.28 (95% CI, 1.06 to 1.56). Consistent with previous studies, a decreased risk of lung cancer was observed among farmers (OR, 0.67; 95% CI, 0.60 to 0.76). The current findings are presented in the context of other recent studies, including discussions of possible causes of farming‐associated excess cancer risk and possible sources of bias.