Environmental/Occupational Epidemiology Research


Environmental and Occupational Epidemiology

The Environmental/Occupational Epidemiology Program prepares students to apply the perspective, theory, and methods of epidemiology to practical and scientific problems related to the relationship of human health to the environment and the workplace. The subject matter embraced by this program is extraordinarily broad, potentially including a wide range of health outcomes and exposures, but usually focusing on the traditionally defined realms of exposures to physical and chemical pollutants in the workplace and in ambient air, water and soil.

Methodological research is also an important activity in the program. Faculty interested in environmental and occupational causes of cancer, for example, are applying advanced laboratory-based techniques to study gene-environment interactions. Methods for the assessment of exposure, including both statistical methodologies and measurement techniques ranging from biological markers to traditional environmental monitoring, are another important area of methodological research for several faculty members, and others are involved with such areas as quantitative risk assessment, meta-analysis, statistical modeling, and the use of geographic information systems (GIS).

This program is designed primarily for students interested in pursuing research careers in academics, government and/or private institutions who will complete the PhD, but individuals with appropriate backgrounds may also pursue the MPH with a concentration in this area.


The primary goal of the Environmental/Occupational Epidemiology Program is to develop new knowledge relevant to the etiology, diagnosis, prognosis, and prevention of health outcomes associated with environmental and occupational exposures using an interdisciplinary epidemiologic approach. The faculty have developed an extensive research program in searching for, and in mitigating, environmental/occupational-related causes of cancer, reproductive outcomes, CVD, and asthma, for example. Recent research activities, with a particular focus on program faculty interactions, are outlined below.

Various research centers across campus also serve as significant resources for our program faculty and students. The UNC-affiliated centers with which program faculty are associated are the following:

Examples of recent facultly publications:


Christy Avery

Whitsel EA and Avery CL . The Environmental Epidemiology of Atrial Arrhythmogenesis: A Research Agenda. Journal of Epidemiology and Community Health 2010; 64(7): 587-90.

Avery CL , Mills KT, Williams R, McGraw KA, Poole C, Smith RL, Whitsel EA. Estimating error in using ambient PM2.5 concentrations as proxies for personal exposures: a review. Epidemiology 2010; 21(2): 215-223.


Avery CL , Mills KT, Williams R, McGraw KA, Poole C, Smith RL, Whitsel EA . Estimating error in using ambient PM2.5 concentrations as proxies for personal exposures: a review. Epidemiology 2010; 21(2): 215-223. BACKGROUND: Studies examining the health effects of particulate matter <or= 2.5 microm in aerodynamic diameter (PM2.5) commonly use ambient PM2.5 concentrations measured at distal monitoring sites as proxies for personal exposure and assume spatial homogeneity of ambient PM2.5. An alternative proxy-the residential outdoor PM2.5 concentration measured adjacent to participant homes-has few advantages under this assumption. OBJECTIVES: We systematically reviewed the correlation between residential outdoor PM2.5 and personal PM2.5 (-rj) as a means of comparing the magnitude and sources of measurement error associated with their use as exposure surrogates. METHODS: We searched seven electronic reference databases for studies of the within-participant residential outdoor-personal PM2.5 correlation. RESULTS: The search identified 567 candidate studies, nine of which were abstracted in duplicate, that were published between 1996 and 2008. They represented 329 nonsmoking participants 6-93 years of age in eight U.S. cities, among whom -rj was estimated (median, 0.53; range, 0.25-0.79) based on a median of seven residential outdoor-personal PM2.5 pairs per participant. We found modest evidence of publication bias (symmetric funnel plot; pBegg = 0.4; pEgger = 0.2); however, we identified evidence of heterogeneity (Cochran’s Q-test p = 0.05). Of the 20 characteristics examined, earlier study midpoints, eastern longitudes, older mean age, higher outdoor temperatures, and lower personal-residential outdoor PM2.5 differences were associated with increased within-participant residential outdoor-personal PM2.5 correlations. CONCLUSIONS: These findings were similar to those from a contemporaneous meta-analysis that examined ambient-personal PM2.5 correlations (rj = median, 0.54; range, 0.09-0.83). Collectively, the meta-analyses suggest that residential outdoor-personal and ambient-personal PM2.5 correlations merit greater consideration when evaluating the potential for bias in studies of PM2.5-mediated health effects.

Carri Casteel

Casteel C, Peek-Asa C, Nocera M, Smith JB, Blando J, Goldmacher S, O’Hagan E, Valiante D, Harrison R. Hospital employee assault rates before and after enactment of the california hospital safety and security act. Ann Epidemiol. 2009 Feb;19(2):125-33.

PURPOSE: This study examines changes in violent event rates to hospital employees before and after enactment of the California Hospital Safety and Security Act in 1995.

METHODS: We compared pre- and post-initiative employee assault rates in California (n = 116) emergency departments and psychiatric units with those in New Jersey (n = 50), where statewide workplace violence initiatives do not exist. Poisson regression with generalized estimating equations was used to compare assault rates between a 3-year pre-enactment period (1993-1995) and a 6-year post-enactment period (1996-2001) using New Jersey hospitals as a temporal control.

RESULTS: Assault rates among emergency department employees decreased 48% in California post-enactment, compared with emergency department employee assault rates in New Jersey (rate ratio [RR] = 0.52, 95% confidence interval [CI]: 0.31, 0.90). Emergency department employee assault rates decreased in smaller facilities (RR = 0.46, 95% CI: 0.21, 0.96) and for-profit-controlled hospitals (RR = 0.39, 95% CI: 0.19, 0.79) post-enactment. Among psychiatric units, for-profit-controlled hospitals (RR = 0.41, 95% CI: 0.19, 0.85) and hospitals located in smaller communities (RR = 0.44, 95% CI: 0.21, 0.92) experienced decreased assault rates post-enactment.

CONCLUSION: Policy may be an effective method to increase safety to health care workers.

Peek-Asa C, Casteel C. Documenting the need for translational research: an example from workplace violence prevention. Injury Prevention 2010;16(1):50-52.

The leading cause of occupational death in small retail establishments–workplace violence–provides an example of how data can be used to document the need for type 2 translational research. First, strategies effective in reducing workplace violence in small retail businesses were identified. Next, the effectiveness of the researched strategies was compared with the types of strategies voluntarily implemented by small businesses. The strongest evidence-based strategies were the least likely to be implemented by businesses, and the relationship between effectiveness and implementation was nearly inverse. For example, cash control policies were found to be effective in 92% of studies, but fewer than 10% of businesses had implemented adequate cash control policies. Surveillance cameras were found to be effective in only 50% of studies, but more than 70% of businesses had implemented them. In the absence of effective translation of knowledge and practice, business owners installed the least effective strategies, often at a higher cost.

Casteel C , Peek-Asa C, Nocera M, Smith JB, Blando J, Goldmacher S, O’Hagan E, Valiante D, Harrison R. Hospital employee assault rates before and after enactment of the California Hospital Safety and Security Act. Annals of Epidemiology 2009;19(2):125-133.

Purpose: This study examines changes in violent event rates to hospital employees before and after enactment of the California Hospital Safety and Security Act in 1995. Methods: We compared pre- and post-initiative employee assault rates in California (n = 116) emergency departments and psychiatric units with those in New Jersey (n = 50), where statewide workplace violence initiatives do not exist. Poisson regression with generalized estimating equations was used to compare assault rates between a 3-year pre-enactment period (1993-1995) and a 6-year post-enactment period (1996-2001) using New Jersey hospitals as a temporal control. Results: Assault rates among emergency department employees decreased 48% in California post-enactment, compared with emergency department employee assault rates in New Jersey (rate ratio [RR] = 0.52, 95% confidence interval [CI]: 0.31, 0.90). Emergency department employee assault rates decreased in smaller facilities (RR = 0.46, 95% CI: 0.21, 0.96) and for-profit-controlled hospitals (RR = 0.39, 95% CI: 0.19, 0.79) post-enactment. Among psychiatric units, for-profit-controlled hospitals (RR = 0.41, 95% CI: 0.19, 0.85) and hospitals located in smaller communities (RR = 0.44, 95% CI: 0.21, 0.92) experienced decreased assault rates post-enactment. Conclusion: Policy may be an effective method to increase safety to health care workers.

Casteel C , Peek-Asa C, Greenland S, Chu LD, Kraus JF. Effectiveness of a workplace violence intervention in small retail and service establishments. Journal of Occupational and Environmental Medicine 2008;50(12):1365-1370.

Objective: Examine the effectiveness of a robbery and violence prevention program in small businesses in Los Angeles. Methods: Gas/convenience, liquor and grocery stores, bars/restaurants, and motels were enrolled between 1997 and 2000. Intervention businesses (n = 305) were provided training, program implementation materials, and recommendations for a comprehensive security program. Control businesses (n = 96) received neither training nor program materials. Results: Rate ratios comparing intervention to control businesses were 0.90 for violent crime (95% confidence limits [CL] = 0.53, 1.53) and 0.81 for robbery (95% CL = 0.38, 1.73). The reduction in violent crime was concentrated in high-compliance intervention businesses (risk ratio = 0.74, 95% CL = 0.40, 1.36). Low-compliance intervention businesses had practically the same postintervention crime as the control businesses. Conclusions: Our results suggest that the workplace violence intervention may reduce violent crime among high-risk businesses, especially those with high program compliance.


Gurka KK, Marshall SW, Runyan CW, Loomis D, Casteel C , Richardson DB. Contrasting robbery-related and non-robbery-related workplace homicides, NC, 1994 – 2003. American Journal of Preventive Medicine 2009;37(1):17-23.

Background: Most research regarding the perpetration of occupational homicide has focused on robbery-related violence; relatively little is known about the circumstances surrounding non-robbery-related occupational homicides and interventions that may prevent these events. A case series was assembled and utilized to examine occupational homicides that were and were not motivated by robbery to determine if select characteristics of the events differed according to the perpetrator’s motivation for the crime and relationship to the workplace. Methods: Information on occupational homicides that occurred in North Carolina from 1994 to 2003 was abstracted from medical examiners’ records and death certificates and was obtained by interviews with law-enforcement officers and from newspaper accounts (data collection occurred in 1996-2001 and 2003-2007). Each homicide was classified by motive and the perpetrator’s relationship to the workplace and its employees. Characteristics of robbery-motivated and non-robbery-motivated homicides were compared. Analysis was conducted in 2006 and 2007. Results: Most occupational homicides occurred during robbery of the workplace (64%). However, 36% of occupational homicides during the study period were not robbery-related. Strangers perpetrated 73% of robbery-related killings but only 11% of non-robbery-related homicides. Homicides unrelated to robbery occurred in several industrial sectors, including retail (28%); service (26%); and manufacturing (22%), whereas robbery-related homicides occurred overwhelmingly in retail (67%). The type of firearm used to perpetrate these killings differed by the perpetrator’s relationship to the workplace. Conclusions: Non-robbery-related homicides constitute a meaningful proportion of occupational homicides, and the characteristics of these cases can differ from those that are robbery-related. The current system by which workplace homicides are classified could be expanded to include robbery motivation. Efforts to examine occupational-homicide-prevention strategies for non-robbery-related homicides are important.

Julie Daniels

Pan IJ, Daniels JL, Goldman BD, Herring AH, Siega-Riz AM, Rogan WJ. Lactational exposure to polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and dichlorodiphenyldichloroethylene and infant neurodevelopment: an analysis of the pregnancy, infection, and nutrition babies study. Environ Health Perspect. 2009 Mar;117(3):488-94.

BACKGROUND: Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) are persistent, bioaccumulative, and toxic pollutants that were broadly used in the United States until the 1970s. Common exposure to PCBs, DDT, and dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of DDT, may influence children’s neurodevelopment, but study results are not consistent. OBJECTIVES: We examined the associations between lactational exposure to PCBs, DDT, and DDE and infant development at 12 months, using data from the Pregnancy, Infection, and Nutrition Babies Study, 2004-2006. METHODS: We measured PCBs, DDT, and DDE in breast milk at the third month postpartum. Lactational exposure of these chemicals was estimated by the product of chemical concentrations and the duration of breast-feeding. Infant development at 12 months of age was measured by the Mullen Scales of Early Learning (n=231) and the Short Form: Level I (infant) of the MacArthur-Bates Communicative Development Indices (n=218). RESULTS: No consistent associations were observed between lactational exposure to PCBs, DDT, and DDE through the first 12 months and the measures of infant development. However, DDE was associated with scoring below average on the gross motor scale of the Mullen among males only (adjusted odds ratio=1.9; 95% confidence interval, 1.1-3.3). CONCLUSION: Infant neurodevelopment at 12 months of age was not impaired by PCBs, DDT, and DDE at the concentrations measured here, in combination with benefits from long duration of breast-feeding in this population.

Braun JM, Daniels JL, Kalkbrenner A, Zimmerman A, Nicholas JS. The effect of maternal smoking during pregnancy on intellectual disabilities among 8-year-old children. Paediatr Perinat Epidemiol. 2009 Sep;23(5):482-91

Prenatal tobacco smoke exposure has been implicated as a risk factor for cognitive deficits in children. The purpose of this study is to examine the association between prenatal tobacco smoke exposure and diagnosis of intellectual disabilities (ID) among 8-year-old children living in Arkansas, Georgia, North Carolina and Utah. In 2002 and 2004, 965 ID case children were identified through a surveillance network and compared with the population of children born in the surveillance region during the same period (n = 104 607). Prenatal tobacco smoke exposure was determined from birth certificates. We estimated the effect of prenatal tobacco smoke exposure (none, <10, 10-19 and ≥20 cigarettes per day) on ID using logistic regression. Generally, the risk of ID was mildly elevated among children whose mothers smoked ≥20 cigarettes per day during pregnancy [RR 1.34; 95% (confidence interval) CI 0.96, 1.87] after adjustment for maternal education, maternal race, maternal age, marital status, child sex, birth year and study site. However, the effect of exposure to ≥20 cigarettes per day significantly differed for males [RR 1.77, 95% CI 1.20, 2.62] compared with females [RR 0.81, 95% CI 0.44, 1.50]. Supplemental analyses reveal substantial confounding of this relationship by socio-economic indicators. A differential effect of tobacco smoke exposure on the risk of ID is suggested for males and females and deserves further investigation; however, the interpretation is tempered by the potential for residual confounding.

Julie Daniels/Andrew Olshan

Cooney MA, Daniels JL, Ross JA, Breslow NE, Pollock BH, Olshan AF. Household pesticides and the risk of Wilms tumor. Environ Health Perspect. 2007 Jan;115(1):134-7.

BACKGROUND: Previous epidemiologic studies have suggested that exposure to pesticides in utero and during early childhood may increase the risk for development of childhood cancer, including Wilms tumor, a childhood kidney tumor. OBJECTIVES: In this analysis we evaluated the role of residential pesticide exposure in relation to the risk of Wilms tumor in children using data from a North American case-control study. METHODS: The National Wilms Tumor Study Group (NWTSG) collected information on exposure to residential pesticides from the month before pregnancy through the diagnosis reference date using detailed phone interviews from 523 case mothers and 517 controls frequency matched on child’s age and geographic region and identified by list-assisted random digit dialing. Pesticides were grouped according to type of pesticide and where they were used. RESULTS: A slightly increased risk of Wilms tumor was found among children of mothers who reported insecticide use [odds ratio (OR) = 1.4, 95% confidence interval (CI), 1.0-1.8; adjusted for education, income, and the matching variables]. Results from all other categories of pesticides were generally close to the null. CONCLUSIONS: This study is the largest case-control study of Wilms tumor to date. We were unable to confirm earlier reports of an increased risk for Wilms tumor among those exposed to residential pesticides during pregnancy through early childhood.

Julie Daniels/Marilie Gammon/David Richardson

Vo TT, Gladen BC, Cooper GS, Baird DD, Daniels JL, Gammon MD, Richardson DB. Dichlorodiphenyldichloroethane and polychlorinated biphenyls: intraindividual changes, correlations, and predictors in healthy women from the southeastern United States. Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2729-36.

Dichlorodiphenyldichloroethane (DDE) and polychlorinated biphenyls (PCB) are widespread environmental contaminants that have been postulated to increase the risk of diseases such as non-Hodgkin’s lymphoma, breast cancer, as well as lead to early menopause. Studies assessing the effect of organochlorine exposure often can only measure organochlorine levels once, such as at study enrollment, which may not be an etiologically relevant time period. We assessed the temporal changes in DDE and PCBs and the predictors of those changes using interview data and DDE and PCB measures collected from 123 women who were enrolled in a baseline study from 1978 to 1982 and followed up in 2003 to 2004. Baseline and follow-up organochlorine levels were compared using Spearman correlations (r(s)), and predictors of the rate of change in log concentration were evaluated using linear regression models. Although serum concentrations dramatically declined (median follow-up to baseline concentration ratio was 16% for DDE and 45% for PCB), baseline and follow-up measures were strongly correlated for DDE (r(s)=0.72) and moderately correlated for PCBs (r(s)=0.43). Prediction of follow-up PCB levels was substantially improved (r(s)=0.75) with data on initial concentration, length of lactation, baseline body mass index, and percent change in body fat, whereas DDE prediction improved slightly (r(s)=0.83) with data on lactation and baseline body mass index. These findings suggest that a single organochlorine measure provides considerable information on relative ranking at distant times and that the predictive power can be improved, particularly for PCBs, with information on a few predictors.

Larry Engel

Purdue MP, Engel LS , Langseth H, Needham LL, Andersen A, Barr DB, Blair A, Rothman N, McGlynn KA. Prediagnostic serum concentrations of organochlorine compounds and risk of testicular germ cell tumors. Environ Health Perspect. 2009 Oct;117(10):1514-9.
BACKGROUND: Recent findings suggest that exposure to organochlorine (OC) compounds, chlordanes and p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE) in particular, may increase the risk of developing testicular germ cell tumors (TGCTs). OBJECTIVE: To further investigate this question, we conducted a nested case-control study of TGCTs within the Norwegian Janus Serum Bank cohort. METHODS: The study was conducted among individuals with serum collected between 1972 and 1978. TGCT cases diagnosed through 1999 (n = 49; 27-62 years of age at diagnosis) were identified through linkage to the Norwegian Cancer Registry. Controls (n =51) were matched to cases on region, blood draw year, and age at blood draw. Measurements of 11 OC insecticide compounds and 34 polychlorinated biphenyl (PCB) congeners were performed using gas chromatography/high-resolution mass spectrometry. Case-control comparisons of lipid-adjusted analyte concentrations were performed using the Wilcoxon signed-rank test. Odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of analyte concentration were calculated using conditional logistic regression. RESULTS: TGCT cases had elevated concentrations of p,p’-DDE (tertile 3 vs. tertile 1 OR (OR(T3)) 2.2; 95% CI, 0.7-6.5; p(Wilcoxon) = 0.07), oxychlordane (OR(T3) 3.2; 95% CI, 0.6-16.8; p(Wilcoxon) = 0.05), trans-nonachlor (OR(T3) 2.6; 95% CI, 0.7-8.9; p(Wilcoxon) = 0.07), and total chlordanes (OR(T3) 2.0; 95% CI, 0.6-7.2; p(Wilcoxon) = 0.048) compared with controls, although no ORs were statistically significant. Seminoma cases had significantly lower concentrations of PCB congeners 44, 49, and 52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 195. CONCLUSIONS: Our study provides additional but qualified evidence supporting an association between exposures to p,p’-DDE and chlordane compounds, and possibly some PCB congeners, and TGCT risk.

Engel LS , Laden F, Andersen A, Strickland PT, Blair A, Needham LL, Barr DB, Wolff MS, Helzlsouer K, Hunter DJ, Lan Q, Cantor KP, Comstock GW, Brock JW, Bush D, Hoover RN, Rothman N. Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin’s lymphoma: a report from three cohorts. Cancer Res. 2007 Jun 1;67(11):5545-52.
The incidence of non-Hodgkin’s lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses’ Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p’-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.

Kamel F, Engel LS , Gladen BC, Hoppin JA, Alavanja MC, Sandler DP. Neurologic symptoms in licensed pesticide applicators in the Agricultural Health Study. Hum Exp Toxicol. 2007 Mar;26(3):243-50.
Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate pesticide levels. We analysed cross-sectional data from 18 782 Caucasian, male, licensed pesticide applicators, enrolled in the Agricultural Health Study from 1993 to 1997. Applicators provided information on lifetime pesticide use, and 23 neurologic symptoms typically associated with pesticide intoxication. Increased risk of experiencing >/=10 symptoms during the year before enrollment was associated with cumulative pesticide use, personally mixing or applying pesticides, pesticide-related medical care, diagnosed pesticide poisoning, and events involving high personal pesticide exposure. Greatest risk was associated with use of organophosphate and organochlorine insecticides. Results were similar after stratification by pesticide use during the year before enrollment, or exclusion of applicators with a history of pesticide poisoning, or high-exposure events. Use of pesticide application methods likely to involve high personal exposure was associated with greater risk. Groups of symptoms reflecting several neurologic domains, including affect, cognition, autonomic and motor function, and vision, were also associated with pesticide exposure. These results suggest that neurologic symptoms are associated with cumulative exposure to moderate levels of organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.

Stephanie Engel

Engel SM , Wetmur J, Chen J, Zhu C, Barr DB, Canfield RL, Wolff MS. “Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood.” Environ Health Perspect. 2011 Aug;119(8):1182-8. Epub 2011 Apr 5.

BACKGROUND: Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates.OBJECTIVE: We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6-9 years.METHODS: The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urine samples were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6-9 (n = 169) years of age. RESULTS: Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QR/RR genotype. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonic trend consistent with greater decrements with increasing prenatal exposure. CONCLUSION: Our findings suggest that prenatal exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects.

Engel SM , Miodovnik A, Canfield RL, Zhu C, Silva MJ, Calafat AM, Wolff MS. Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ Health Perspect. 2010 Apr;118(4):565-71. Epub 2010 Jan 8.

BACKGROUND: Experimental and observational studies have reported biological consequences of phthalate exposure relevant to neurodevelopment. OBJECTIVE: Our goal was to examine the association of prenatal phthalate exposure with behavior and executive functioning at 4-9 years of age. METHODS: The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urines were collected and analyzed for phthalate metabolites. Children (n = 188, n = 365 visits) were assessed for cognitive and behavioral development between the ages of 4 and 9 years. RESULTS: In multivariate adjusted models, increased loge concentrations of low molecular weight (LMW) phthalate metabolites were associated with poorer scores on the aggression [beta = 1.24; 95% confidence interval (CI), 0.15- 2.34], conduct problems (beta = 2.40; 95% CI, 1.34-3.46), attention problems (beta = 1.29; 95% CI, 0.16- 2.41), and depression (beta = 1.18; 95% CI, 0.11-2.24) clinical scales; and externalizing problems (beta = 1.75; 95% CI, 0.61-2.88) and behavioral symptom index (beta = 1.55; 95% CI, 0.39-2.71) composite scales. Increased loge concentrations of LMW phthalates were also associated with poorer scores on the global executive composite index (beta = 1.23; 95% CI, 0.09-2.36) and the emotional control scale (beta = 1.33; 95% CI, 0.18- 2.49). CONCLUSION: Behavioral domains adversely associated with prenatal exposure to LMW phthalates in our study are commonly found to be affected in children clinically diagnosed with conduct or attention deficit hyperactivity disorders.

Marilie Gammon

Mordukhovich I, Rossner P Jr, Terry MB, Santella R, Zhang YJ, Hibshoosh H, Memeo L, Mansukhani M, Long CM, Garbowski G, Agrawal M, Gaudet MM, Steck SE, Sagiv SK, Eng SM, Teitelbaum SL, Neugut AI, Conway-Dorsey K, Gammon MD . Associations between polycyclic aromatic hydrocarbon-related exposures and p53 mutations in breast tumors. Environ Health Perspect. 2010 Apr;118(4):511-8. PMID: 20064791

BACKGROUND: Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology. Objectives: We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number. METHODS: We examined this possibility in a population-based case-control study using polytomous logistic regression. As previously reported, 151 p53 mutations among 859 tumors were identified using Surveyor nuclease and confirmed by sequencing. RESULTS: We found that participants with p53 mutations were less likely to be exposed to PAHs (assessed by smoking status in 859 cases and 1,556 controls, grilled/smoked meat intake in 822 cases and 1,475 controls, and PAH-DNA adducts in peripheral mononuclear cells in 487 cases and 941 controls) than participants without p53 mutations. For example, active and passive smoking was associated with p53 mutation-negative [odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.11-2.15] but not p53 mutation-positive (OR = 0.77; 95% CI, 0.43-1.38) cancer (ratio of the ORs = 0.50, p < 0.05). However, frameshift mutations, mutation number, G:C–>A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects. CONCLUSIONS: These findings suggest that PAHs may be associated with specific breast tumor p53 mutation subgroups rather than with overall p53 mutations and may also be related to breast cancer through mechanisms other than p53 mutation.

McCarty KM, Santella RM, Steck SE, Cleveland RJ, Ahn J, Ambrosone CB, North K, Sagiv SK, Eng SM, Teitelbaum SL, Neugut AI, Gammon MD. PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk. Environ Health Perspect. 2009 Apr;117(4):552-8.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker. OBJECTIVE: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoking. METHODS: We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973). RESULTS: Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively). CONCLUSION: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.

Steve Marshall

Kucera KL, Loomis D, Lipscomb H, Marshall SW. Prospective study of incident injuries among southeastern United States commercial fishermen. Occup Environ Med. 2010 Dec;67(12):829-36.

OBJECTIVE: The purpose of this study was to describe occupational exposures and the incidence of non-fatal injuries among a group of southeastern US small-scale fishermen.

METHODS: Participants (n=219) were enrolled in a prospective cohort study and followed from August 1999 to May 2002. Demographic information was obtained at baseline, and weekly and biweekly telephone interviews elicited information on number of days worked, fishery, fishing gear used, maintenance work, glove use and any work-related injury events. Incidence rate ratios (IRR) and 95% CIs were calculated with Poisson regression for each factor and multivariate models controlled for potential confounders.

RESULTS: Over a third of participants (81/217) reported 125 injury events over 46 153 work-days for rate of 2.74 per 1000 work-days (95% CI 2.19 to 3.41). The majority of injuries were penetrating wounds to the hand, thumb and finger (35%) or back sprains and strains (8%); most required no medical care or time off work (67%). Injury rates were similar for on and off the water work (1.9 per 1000 work-days). Injury rates differed by fishery, water location and month. Factors associated with an increased injury rate included working on someone else’s boat and maintenance work. Glove use was protective.

CONCLUSION: Similar injury characteristics were observed in small-scale fishing as compared to large-scale. For small-scale fishermen, off and on the water work locations, and particularly maintenance work, were important predictors of injury. Despite the protective association for glove use, penetrating wounds to the hand, thumb and finger were common.

Steve Marshall/Julie Daniels

Kucera KL, Loomis D, Lipscomb HJ, Marshall SW, Mirka GA, Daniels JL. Ergonomic risk factors for low back pain in North Carolina crab pot and gill net commercial fishermen. Am J Ind Med. 2009 Apr;52(4):311-21.

BACKGROUND: The objective of this research was to determine the association between LBP that limited or interrupted fishing work and ergonomic low back stress measured by (1) self-reported task and (2) two ergonomic assessment methods of low back stress. METHODS: Eligible participants were from a cohort of North Carolina commercial fishermen followed for LBP in regular clinic visits from 1999 to 2001 (n = 177). Work history, including crab pot and gill net fishing task frequency, was evaluated in a telephone questionnaire (n = 105). Ergonomic exposures were measured in previous study of 25 fishermen using two methods. The occurrence rate of LBP that limited or interrupted fishing work since last visit (severe LBP) was evaluated in a generalized Poisson regression model. RESULTS: Predictors of severe LBP included fishing with crew members and a previous history of severe LBP. Among crab pot and gill net fishermen (n = 89), running pullers or net reels, sorting catch, and unloading catch were associated with an increased rate of LBP. Percent of time in forces >20 lb while in non-neutral trunk posture, spine compression >3,400 N, and National Institute of Occupational Safety and Health lifting indices >3.0 were associated with LBP. CONCLUSIONS: Tasks characterized by higher (unloading boat and sorting catch) and lower (running puller or net reel) ergonomic low back stress were associated with the occurrence of severe LBP. History of LBP, addition of crew members, and self-selection out of tasks were likely important contributors to the patterns of low back stress and outcomes we observed. Based on the results of this study, a participatory ergonomic intervention study is currently being conducted to develop tools and equipment to decrease low back stress in commercial crab pot fishing.

Steve Marshall/David Richardson

Gurka KK, Marshall SW, Runyan CW, Loomis DP, Casteel C, Richardson DB. Contrasting robbery- and non-robbery-related workplace homicide: North Carolina, 1994-2003. Am J Prev Med. 2009 Jul;37(1):17-23.

BACKGROUND: Most research regarding the perpetration of occupational homicide has focused on robbery-related violence; relatively little is known about the circumstances surrounding non-robbery-related occupational homicides and interventions that may prevent these events. A case series was assembled and utilized to examine occupational homicides that were and were not motivated by robbery to determine if select characteristics of the events differed according to the perpetrator’s motivation for the crime and relationship to the workplace. METHODS: Information on occupational homicides that occurred in North Carolina from 1994 to 2003 was abstracted from medical examiners’ records and death certificates and was obtained by interviews with law-enforcement officers and from newspaper accounts (data collection occurred in 1996-2001 and 2003-2007). Each homicide was classified by motive and the perpetrator’s relationship to the workplace and its employees. Characteristics of robbery-motivated and non-robbery-motivated homicides were compared. Analysis was conducted in 2006 and 2007. RESULTS: Most occupational homicides occurred during robbery of the workplace (64%). However, 36% of occupational homicides during the study period were not robbery-related. Strangers perpetrated 73% of robbery-related killings but only 11% of non-robbery-related homicides. Homicides unrelated to robbery occurred in several industrial sectors, including retail (28%); service (26%); and manufacturing (22%), whereas robbery-related homicides occurred overwhelmingly in retail (67%). The type of firearm used to perpetrate these killings differed by the perpetrator’s relationship to the workplace. CONCLUSIONS: Non-robbery-related homicides constitute a meaningful proportion of occupational homicides, and the characteristics of these cases can differ from those that are robbery-related. The current system by which workplace homicides are classified could be expanded to include robbery motivation. Efforts to examine occupational-homicide-prevention strategies for non-robbery-related homicides are important.

Steve Marshall/Steve Wing

Mirabelli MC, Wing S, Marshall SW, Wilcosky TC. Asthma symptoms among adolescents who attend public schools that are located near confined swine feeding operations. Pediatrics 2006 Jul;118(1):e66-75.

OBJECTIVES: Little is known about the health effects of living in close proximity to industrial swine operations. We assessed the relationship between estimated exposure to airborne effluent from confined swine feeding operations and asthma symptoms among adolescents who were aged 12 to 14 years. METHODS: During the 1999-2000 school year, 58169 adolescents in North Carolina answered questions about their respiratory symptoms, allergies, medications, socioeconomic status, and household environments. To estimate the extent to which these students may have been exposed during the school day to air pollution from confined swine feeding operations, we used publicly available data about schools (n = 265) and swine operations (n = 2343) to generate estimates of exposure for each public school. Prevalence ratios and 95% confidence intervals for wheezing within the past year were estimated using random-intercepts binary regression models, adjusting for potential confounders, including age, race, socioeconomic status, smoking, school exposures, and household exposures. RESULTS: The prevalence of wheezing during the past year was slightly higher at schools that were estimated to be exposed to airborne effluent from confined swine feeding operations. For students who reported allergies, the prevalence of wheezing within the past year was 5% higher at schools that were located within 3 miles of an operation relative to those beyond 3 miles and 24% higher at schools in which livestock odor was noticeable indoors twice per month or more relative to those with no odor. CONCLUSIONS: Estimated exposure to airborne pollution from confined swine feeding operations is associated with adolescents’ wheezing symptoms.

Jennifer M. Norton, Steve Wing, Hester J. Lipscomb, Jay S. Kaufman, Stephen W. Marshall, and Altha J. Cravey. Race, Wealth, and Solid Waste Facilities in North Carolina. Environ Health Perspect. 2007 September; 115(9): 1344-1350.

BACKGROUND. Concern has been expressed in North Carolina that solid waste facilities may be disproportionately located in poor communities and in communities of color, that this represents an environmental injustice, and that solid waste facilities negatively impact the health of host communities. OBJECTIVE. Our goal in this study was to conduct a statewide analysis of the location of solid waste facilities in relation to community race and wealth. METHODS. We used census block groups to obtain racial and economic characteristics, and information on solid waste facilities was abstracted from solid waste facility permit records. We used logistic regression to compute prevalence odds ratios for 2003, and Cox regression to compute hazard ratios of facilities issued permits between 1990 and 2003. RESULTS. The adjusted prevalence odds of a solid waste facility was 2.8 times greater in block groups with ≥50% people of color compared with block groups with < 10% people of color, and 1.5 times greater in block groups with median house values < $60,000 compared with block groups with median house values ≥$100,000. Among block groups that did not have a previously permitted solid waste facility, the adjusted hazard of a new permitted facility was 2.7 times higher in block groups with ≥50% people of color compared with block groups with < 10% people of color. CONCLUSION. Solid waste facilities present numerous public health concerns. In North Carolina solid waste facilities are disproportionately located in communities of color and low wealth. In the absence of action to promote environmental justice, the continued need for new facilities could exacerbate this environmental injustice.

Andrew Olshan

Hoffman CS, Mendola P, Savitz DA, Herring AH, Loomis D, Hartmann KE, Singer PC, Weinberg HS, Olshan AF. Drinking water disinfection by-product exposure and duration of gestation. Epidemiology. 2008 Sep;19(5):738-46.

BACKGROUND: Recent studies suggest elevated exposure to drinking water disinfection by-products (DBPs) may be associated with decreased risk of preterm birth. We examined this association for exposure to total trihalomethanes (TTHMs), 5 haloacetic acids (HAA5), and total organic halides. METHODS: Analysis included 2039 women in a prospective pregnancy study conducted from 2000 through 2004 in 3 study sites. Water samples were collected and analyzed for DBP concentrations. Participant data were collected through interviews, an early ultrasound, and birth records. We assessed the associations between DBPs and preterm birth (<37-weeks’ gestation) using log-binomial regression. Discrete-time hazard analysis was used to model the conditional odds of delivery each week in relation to DBP exposure. RESULTS: Average second trimester DBP levels were associated with lower risk of preterm birth. Adjusted risk ratios for TTHM levels of 33.1-55.0, 55.1-66.3, 66.4-74.8, and 74.9-108.8 microg/L versus 2.2-4.6 microg/L were 0.8 (95% confidence intervals = 0.5-1.3), 0.9 (0.6-1.4), 0.7 (0.4-1.1), and 0.5 (0.3-0.9), respectively. Risk ratios for HAA5 levels of 17.9-22.0, 22.1-31.5, 31.6-40.4, and 40.5-52.8 microg/L versus 0-0.9 microg/L were 1.1 (0.8-1.7), 0.8 (0.5-1.2), 0.5 (0.3-0.8), and 0.7 (0.4-1.1), respectively. The conditional odds of delivery each week were decreased for the highest TTHM and HAA5 exposure groups versus the low exposure group for gestational weeks 33-40. CONCLUSIONS: The probability of preterm birth was not increased with high DBP exposure.

Luben TJ, Olshan AF, Herring AH, Jeffay S, Strader L, Buus RM, Chan RL, Savitz DA, Singer PC, Weinberg HS, Perreault SD. The healthy men study: an evaluation of exposure to disinfection by-products in tap water and sperm quality. Environ Health Perspect. 2007 Aug;115(8):1169-76.

BACKGROUND: Chlorination of drinking water generates disinfection by-products (DBPs), which have been shown to disrupt spermatogenesis in rodents at high doses, suggesting that DBPs could pose a reproductive risk to men. In this study we assessed DBP exposure and testicular toxicity, as evidenced by altered semen quality. METHODS: We conducted a cohort study to evaluate semen quality in men with well-characterized exposures to DBPs. Participants were 228 presumed fertile men with different DBP profiles. They completed a telephone interview about demographics, health history, water consumption, and other exposures and provided a semen sample. Semen outcomes included sperm concentration and morphology, as well as DNA integrity and chromatin maturity. Exposures to DBPs were evaluated by incorporating data on water consumption and bathing and showering with concentrations measured in tap water. We used multivariable linear regression to assess the relationship between exposure to DBPs and adverse sperm outcomes. RESULTS: The mean (median) sperm concentration and sperm count were 114.2 (90.5) million/mL and 362 (265) million, respectively. The mean (median) of the four trihalomethane species (THM4) exposure was 45.7 (65.3) microg/L, and the mean (median) of the nine haloacetic acid species (HAA9) exposure was 30.7 (44.2) microg/L. These sperm parameters were not associated with exposure to these classes of DBPs. For other sperm outcomes, we found no consistent pattern of increased abnormal semen quality with elevated exposure to trihalomethanes (THMs) or haloacetic acids (HAAs). The use of alternate methods for assessing exposure to DBPs and site-specific analyses did not change these results. CONCLUSIONS: The results of this study do not support an association between exposure to levels of DBPs near or below regulatory limits and adverse sperm outcomes in humans.

Charles Poole

Braun JM, Daniels JL, Poole C , Olshan AF, Hornung R, Bernert JT, Xiu Y, Bearer C, Boyd DB, Lanphear BP. A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium cotinine and their association with infant birth weight. Environmental Health 2010 Aug 27;9:53. PMID 20799929.

Background: The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure.
Methods: We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3′-hydroxycotinine concentrations) and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression.
Results: We detected nicotine (80%), cotinine (69%), and trans-3′-hydroxycotinine (57%) in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight.
Conclusions: Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.

Braun JM, Daniels JL, Poole C , Olshan AF, Hornung R, Bernert JT, Khoury J, Needham LL, Barr DB, Lanphear BP. Prenatal environmental tobacco smoke exposure and early childhood body mass index. Paediatric and Perinatal Epidemiology 2010; 24: 524-534.

Maternal smoking during pregnancy is associated with increased risk of childhood overweight body mass index (BMI). Less is known about the association between prenatal secondhand tobacco smoke (SHS) exposure and childhood BMI. We followed 292 mother-child dyads from early pregnancy to 3 years of age. Prenatal tobacco smoke exposure during pregnancy was quantified using self-report and serum cotinine biomarkers. We used linear mixed models to estimate the association between tobacco smoke exposure and BMI at birth, 4 weeks, and 1, 2 and 3 years. During pregnancy, 15% of women reported SHS exposure and 12% reported active smoking, but 51% of women had cotinine levels consistent with SHS exposure and 10% had cotinine concentrations indicative of active smoking. After adjustment for confounders, children born to active smokers (self-report or serum cotinine) had higher BMI at 2 and 3 years of age, compared with unexposed children. Children born to women with prenatal serum cotinine concentrations indicative of SHS exposure had higher BMI at 2 (mean difference [MD] 0.3 [95% confidence interval −0.1, 0.7]) and 3 (MD 0.4 [0, 0.8]) years compared with unexposed children. Using self-reported prenatal exposure resulted in non-differential exposure misclassification of SHS exposures that attenuated the association between SHS exposure and BMI compared with serum cotinine concentrations. These findings suggest active and secondhand prenatal tobacco smoke exposure may be related to an important public health problem in childhood and later life. In addition, accurate quantification of prenatal secondhand tobacco smoke exposures is essential to obtaining valid estimates.

Williamson DM, White MC, Poole C, Kleinbaum D, Vogt R, North K. Evaluation of serum immunoglobulins among individuals living near six Superfund sites. Environ Health Perspect. 2006 Jul;114(7):1065-71.

Residents living in communities near Superfund sites have expressed concern that releases from these facilities affect their health, including adverse effects on their immune systems. We used data from six cross-sectional studies to evaluate whether people who live near several Superfund sites are more likely to have individual immunoglobulin test results (IgA, IgG, and IgM) below or above the reference range than those who live in comparison areas with no Superfund site. Study participants consisted of target-area residents who lived close to a Superfund site and comparison-area residents who were not located near any Superfund or hazardous waste sites. A consistent modeling strategy was used across studies to assess the magnitude of the relationship between area of residence and immunoglobulin test results, adjusting for potential confounders and effect modifiers. In all study areas, the results suggest that people who live near a Superfund site may have been more likely to have IgA test results above the reference range than comparison areas residents regardless of modeling strategy employed. The effect measures were larger for residents who lived in communities near military bases with groundwater contamination. For all analyses the wide confidence intervals reflect uncertainty in the magnitude of these effects. To adequately address the question of whether the immune system is affected by low-level exposures to hazardous substances, we recommend that more functional immunotoxicity tests be conducted in human populations where individual exposure information is available or when it can be reasonably estimated from environmental exposure measurements.

Sagiv SK, Mendola P, Loomis D, Herring AH, Neas LM, Savitz DA, Poole C. A time-series analysis of air pollution and preterm birth in Pennsylvania, 1997-2001. Environ Health Perspect. 2005 May;113(5):602-6.

Preterm delivery can lead to serious infant health outcomes, including death and lifelong disability. Small increases in preterm delivery risk in relation to spatial gradients of air pollution have been reported, but previous studies may have controlled inadequately for individual factors. Using a time-series analysis, which eliminates potential confounding by individual risk factors that do not change over short periods of time, we investigated the effect of ambient outdoor particulate matter with diameter < or = 10 microm (PM10) and sulfur dioxide on risk for preterm delivery. Daily counts of preterm births were obtained from birth records in four Pennsylvania counties from 1997 through 2001. We observed increased risk for preterm delivery with exposure to average PM10 and SO2 in the 6 weeks before birth [respectively, relative risk (RR) = 1.07; 95% confidence interval (CI), 0.98-1.18 per 50 microg/m3 increase; RR = 1.15; 95% CI, 1.00-1. 32 per 15 ppb increase], adjusting for long-term preterm delivery trends, co-pollutants, and offsetting by the number of gestations at risk. We also examined lags up to 7 days before the birth and found an acute effect of exposure to PM10 2 days and 5 days before birth (respectively, RR = 1.10; 95% CI, 1.00-1.21; RR = 1.07; 95% CI, 0.98-1.18) and SO2 3 days before birth (RR = 1.07; 95% CI, 0.99-1.15), adjusting for covariates, including temperature, dew point temperature, and day of the week. The results from this time-series analysis, which provides evidence of an increase in preterm birth risk with exposure to PM10 and SO2, are consistent with prior investigations of spatial contrasts.

Perinatal Exposure to Hazardous Air Pollutants and Autism Spectrum Disorders at Age 8.
Kalkbrenner AE, Daniels JL, Chen JC, Poole C , Emch M, Morrissey J.

BACKGROUND: Hazardous air pollutants are plausible candidate exposures for autism spectrum disorders. They have been explored in recent studies for their role in the development of these disorders.
METHODS: We used a prevalent case-control design to screen perinatal exposure to 35 hazardous air pollutants for further investigation in autism etiology. We included 383 children with autism spectrum disorders and, as controls, 2,829 children with speech and language impairment. All participants were identified from the records-based surveillance of 8-year-old children conducted by the Autism and Developmental Disabilities Monitoring Network in North Carolina (for children born in 1994 and 1996) and West Virginia (born in 1992 and 1994). Exposures to ambient concentrations of metal, particulate, and volatile organic air pollutants in the census tract of the child’s birth residence were assigned from the 1996 National Air Toxics Assessment annual-average model. We estimated odds ratios (ORs) for autism spectrum disorders and corresponding 95% confidence intervals (CIs), comparing across the 20th and 80th percentiles of log-transformed hazardous air pollutant concentration among the selected controls, using semi-Bayes logistic models and adjusting for sampling variables (surveillance year and state), a priori demographic confounders from the birth certificate and census, and covarying air pollutants.
RESULTS: We estimated many near-null ORs, including those for metals, established human neurodevelopmental toxicants, and several pollutants that were elevated in a similar study in California. Hazardous air pollutants with more precise and elevated OR estimates included methylene chloride, 1.4 (95% CI = 0.7-2.5), quinoline, 1.4 (1.0-2.2), and styrene, 1.8 (1.0-3.1).
CONCLUSIONS: Our screening design was limited by exposure misclassification of air pollutants and the use of an alternate developmental disorder as the control group, both of which may have biased results toward the null. Despite these limitations, methylene chloride, quinoline, and styrene emerged (based on this analysis and prior epidemiologic evidence) as candidates that warrant further investigation for a possible role in autism etiology.

David Richardson

Richardson DB. Latency models for analyses of protracted exposures. Epidemiology 2009 May;20(3):395-9.

The effect of an increment of exposure on disease risk may vary with time-since-exposure. If the pattern of temporal variation is simple (eg, a peak and then a decline in excess risk of disease) then this may be modeled efficiently via a parametric latency function. Estimation of the parameters for such a model can be difficult because the parameters are not a function of a simple summary of the exposure history. Typically, such parameters are estimated via an iterative search that requires calculating a different time-weighted exposure for each combination of the latency function parameters. This article describes a simple approach to fitting logistic regression models that include a parametric latency function. This approach is illustrated using data from a study of the association between radon exposure and lung cancer mortality among underground uranium miners. This approach should facilitate fitting models to assess variation with time since exposure in the effect of a protracted environmental or occupational exposure.

David Richardson/Steve Wing

Wing S , Richardson DB , Hoffmann W. Cancer risks near nuclear facilities: The importance of research design and explicit study hypotheses. Environmental Health Perspectives, 119:417-21, 2011. BACKGROUND: In April 2010, the U.S. Nuclear Regulatory Commission asked the National Academy of Sciences to update a 1990 study of cancer risks near nuclear facilities. Prior research on this topic has suffered from problems in hypothesis formulation and research design. OBJECTIVES: We review epidemiologic principles used in studies of generic exposure-response associations and in studies of specific sources of exposure. We then describe logical problems with assumptions, formation of testable hypotheses, and interpretation of evidence in previous research on cancer risks near nuclear facilities. DISCUSSION: Advancement of knowledge about cancer risks near nuclear facilities depends on testing specific hypotheses grounded in physical and biological mechanisms of exposure and susceptibility while considering sample size and ability to adequately quantify exposure, ascertain cancer cases, and evaluate plausible confounders. CONCLUSIONS: Next steps in advancing knowledge about cancer risks near nuclear facilities require studies of childhood cancer incidence, focus on in utero and early childhood exposures, use of specific geographic information, and consideration of pathways for transport and uptake of radionuclides. Studies of cancer mortality among adults, cancers with long latencies, large geographic zones, and populations that reside at large distances from nuclear facilities are better suited for public relations than for scientific purposes.

Richardson DB, Sugiyama H, Wing S, Sakata R, Grant E, Shimizu Y, Nishi N, Geyer S, Soda M, Suyama A, Kasagi F, Kodama K. Positive associations between ionizing radiation and lymphoma mortality among men. Am J Epidemiol. 2009 Apr 15;169(8):969-76.

The authors investigated the relation between ionizing radiation and lymphoma mortality in 2 cohorts: 1) 20,940 men in the Life Span Study, a study of Japanese atomic bomb survivors who were aged 15-64 years at the time of the bombings of Hiroshima and Nagasaki, and 2) 15,264 male nuclear weapons workers who were hired at the Savannah River Site in South Carolina between 1950 and 1986. Radiation dose-mortality trends were evaluated for all malignant lymphomas and for non-Hodgkin’s lymphoma. Positive associations between lymphoma mortality and radiation dose under a 5-year lag assumption were observed in both cohorts (excess relative rates per sievert were 0.79 (90% confidence interval: 0.10, 1.88) and 6.99 (90% confidence interval: 0.96, 18.39), respectively). Exclusion of deaths due to Hodgkin’s disease led to small changes in the estimates of association. In each cohort, evidence of a dose-response association was primarily observed more than 35 years after irradiation. These findings suggest a protracted induction and latency period for radiation-induced lymphoma mortality.

Richardson DB, Wing S. Leukemia Mortality among Workers at the Savannah River Site. Am J Epidemiol 2007;166: 1015-1022.

The authors investigated associations between ionizing radiation and leukemia mortality among workers at the Savannah River Site (South Carolina). A total of 18,883 workers hired between 1950 and 1986 were followed through 2002 to ascertain causes of death. Estimates of radiation doses from external sources and internal tritium uptakes were derived from dosimetry records through 1999. Radiation dose-mortality trends were evaluated for leukemia, leukemia excluding chronic lymphocytic leukemia, and myeloid leukemia. A positive association was observed between leukemia mortality and radiation dose under a 3-year lag assumption (excess relative rate/10 mSv = 0.04, 90% confidence interval: -0.00, 0.12). The association was of larger magnitude for leukemia excluding chronic lymphocytic leukemia (excess relative rate/10 mSv = 0.08, 90% confidence interval: 0.01, 0.20) and myeloid leukemia (excess relative rate/10 mSv = 0.12, 90% confidence interval: 0.02, 0.35). Compared with males, females had less complete dosimetry information; when analyses were restricted to males, the estimated association for each cause of death increased slightly in magnitude and goodness of fit. Exposures accrued 3-15 years prior were more strongly related to leukemia than exposures in the more distant past. This study provides evidence of positive associations between radiation dose and leukemia mortality among Savannah River Site workers. The temporal patterns of association appear consistent with those in studies of populations exposed at higher dose rates.

Melissa Troester

Troester MA, Swift-Scanlan T. Challenges in studying the etiology of breast cancer subtypes. Breast Cancer Res. 2009;11(3):104.

Research that classifies breast tumors into homogenous subgroups could ultimately help to define public health prevention strategies for aggressive breast cancer subtypes. However, etiologic research on molecular breast cancer subtypes must overcome several challenges. Stratifying breast cancers into subgroups can reduce statistical power and, therefore, may require non-traditional analytical methods. Integrating results across studies is hampered by varying definitions of molecular subtypes, with some studies using triple negative status and others using specific markers to define basal-like cancers. In addition, triple negative and basal-like breast cancers appear to show strong associations with race, so the varied racial and ethnic composition of different datasets can make comparison across studies challenging. In spite of these challenges, some strong and consistent associations between triple negative or basal-like breast cancer and demographic variables are emerging, and there are hints that prevention strategies for this aggressive subtype of breast cancer may also be attainable.

Troester MA, Herschkowitz JI, Oh DS, He X, Hoadley KA, Barbier CS, Perou CM. Gene expression patterns associated with p53 status in breast cancer. BMC Cancer. 2006 Dec 6;6:276.

BACKGROUND: Breast cancer subtypes identified in genomic studies have different underlying genetic defects. Mutations in the tumor suppressor p53 occur more frequently in estrogen receptor (ER) negative, basal-like and HER2-amplified tumors than in luminal, ER positive tumors. Thus, because p53 mutation status is tightly linked to other characteristics of prognostic importance, it is difficult to identify p53′s independent prognostic effects. The relation between p53 status and subtype can be better studied by combining data from primary tumors with data from isogenic cell line pairs (with and without p53 function). METHODS: The p53-dependent gene expression signatures of four cell lines (MCF-7, ZR-75-1, and two immortalized human mammary epithelial cell lines) were identified by comparing p53-RNAi transduced cell lines to their parent cell lines. Cell lines were treated with vehicle only or doxorubicin to identify p53 responses in both non-induced and induced states. The cell line signatures were compared with p53-mutation associated genes in breast tumors. RESULTS: Each cell line displayed distinct patterns of p53-dependent gene expression, but cell type specific (basal vs. luminal) commonalities were evident. Further, a common gene expression signature associated with p53 loss across all four cell lines was identified. This signature showed overlap with the signature of p53 loss/mutation status in primary breast tumors. Moreover, the common cell-line tumor signature excluded genes that were breast cancer subtype-associated, but not downstream of p53. To validate the biological relevance of the common signature, we demonstrated that this gene set predicted relapse-free, disease-specific, and overall survival in independent test data. CONCLUSION: In the presence of breast cancer heterogeneity, experimental and biologically-based methods for assessing gene expression in relation to p53 status provide prognostic and biologically-relevant gene lists. Our biologically-based refinements excluded genes that were associated with subtype but not downstream of p53 signaling, and identified a signature for p53 loss that is shared across breast cancer subtypes.

Eric Whitsel/Charlie Poole

Avery CL, Mills KT, Williams R, McGraw KA, Poole C, Smith RL, Whitsel EA. Estimating error in using ambient PM2.5 concentrations as proxies for personal exposures: The Environmental Epidemiology Arrhythmogenesis in the Women’s Health nitiative. Epidemiology 2009; in press.

Background: Several methods have been used to account for measurement error inherent in using the ambient concentration of particulate matter < 2.5 µm (PM2.5, ug/m3) as a proxy for personal exposure. Common features of such methods are their reliance on the estimated correlation between ambient and personal PM2.5 concentrations (r). However, extant studies of r have not been systematically and quantitatively assessed for publication bias or heterogeneity. Methods: We searched seven electronic reference databases for studies of the within-participant, ambient-personal PM2.5 correlation. Results: The search identified 567 candidate studies, eighteen (3%) of which met inclusion criteria and were abstracted by two co-authors. The studies were published between 1999 and 2008. They represented 619 non-smoking participants aged 6-93 years in seventeen European and North American cities among whom r (Pearson 37%; median 0.54; range 0.09, 0.83) was estimated based on a median of eight ambient-personal PM2.5 pairs per participant (range 5, 20) collected over 27 to 547 days. Overall, there was little evidence for publication bias (funnel plot symmetry tests: Begg’s log rank test P=0.9; Egger’s regression asymmetry test P=0.2); however strong evidence for heterogeneity was noted (PCochran < 0.001). Of the twenty characteristics examined, European locales, eastern longitudes in North America, higher ambient PM2.5 concentrations, higher relative humidity, and lower between-participant variation in r were associated with increased r. Conclusions: Collectively, these findings suggest that characteristics of participants, studies and the environments in which they are conducted may affect the accuracy of ambient PM2.5 as a proxy for personal exposure.


Whitsel EA and Avery C L. The Environmental Epidemiology of Atrial Arrhythmogenesis: A Research Agenda. Journal of Epidemiology and Community Health 2010; 64(7): 587-90. Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice, and makes an important contribution to cardiovascular disease (CVD) and all-cause mortality. The focus of AF research has recently shifted, from concentrating on treatments and complications, to the evaluation of putative risk factors including ambient air pollution. Although the present study pertains specifically to AF, much of its content is drawn from, and therefore is applicable to, the study of other arrhythmias, the conduct of which is confronted by many of the same challenges. Meeting these challenges involves recognising the collective importance of 1. large, ethnically and geographically diverse, clinically well-characterised populations; 2. methods for reducing uncertainty in outcome ascertainment, distinguishing effects of pervasive environmental exposures and improving their estimation; 3. approaches to evaluation of susceptibility; and 4. strategies for informing regulatory policies designed to help control population-level risks for CVD.

Eric Whitsel

Whitsel EA, Quibrera PM, Christ SL, Liao D, Prineas RJ, Anderson GL, Heiss G. Heart rate variability, ambient particulate matter air pollution, and glucose homeostasis: the environmental epidemiology of arrhythmogenesis in the women’s health initiative. Am J Epidemiol. 2009 Mar 15;169(6):693-703.

Metabolic neuropathophysiology underlying the prediabetic state may confer susceptibility to the adverse health effects of ambient particulate matter

Zhang ZM, Whitsel EA, Quibrera PM, Smith RL, Liao D, Anderson GL, Prineas RJ. Ambient fine particulate matter exposure and myocardial ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI) study. Environ Health Perspect. 2009 May;117(5):751-6.

BACKGROUND: Ambient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated. METHODS: We studied the association between PM and ischemia among 57,908 Women’s Health Initiative clinical trial participants from 1999-2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiograms (ECGs). We used U.S. Environmental Protection Agency’s monitor data to estimate concentrations of PM < 2.5 microm (PM2.5) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration > or = 120 msec. RESULTS: Overall, 6% of the remaining 55,529 women (52-90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from -14 to 349 microV). PM2.5 (mean +/- SD) averaged over lag(0-2) was 14 +/- 7 µg/m3. In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-µg/m3 increase in lag(0-2) PM2.5 was associated with a 4% [95% confidence interval (CI), -3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of -2 µV (95% CI, -5 to 0 µV) in lead V3. CONCLUSIONS: Short-term PM2.5 exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST-T abnormalities and decreases in T amplitude.

Steven Wing Research interests: Environmental justice; ionizing radiation; industrial animal production; built environment.

Keil A, Wing S , Lowman A. Suitability of public records for evaluating health effects of treated sewage sludge in North Carolina. North Carolina Medical Journal, 72:98-104, 2011.

Wing S , Richardson DB, Hoffmann W. Cancer risks near nuclear facilities: The importance of research design and explicit study hypotheses. Environmental Health Perspectives, 119:417-21, 2011.

Stingone J, Wing S . Poultry-litter incineration as a source of energy: Reviewing the potential for impacts on environmental health and justice. New Solutions, 21:27-42, 2011.

Schinasi L, Horton RA, Guidry VT, Wing S , Marshall SW, Morland KB. Air pollution, lung function, and physical symptoms in communities near concentrated swine-feeding operations. Epidemiology, 20:208-15, 2011.

Angelon-Gaetz K, Richardson DB, Wing S . Inequalities in the nuclear age: Impact of race and gender on radiation exposure at the Savannah River Site (1951-1999). New Solutions. 20:195-210, 2010.

Wing S. Ethics for environmental health research: The case of the U.S. nuclear weapons industry. New Solutions. 20:179-187, 2010.

Schinasi L, Horton RA, Wing S. Data completeness and quality in a community-based and participatory epidemiologic study. Progress in Community Partnerships: Research Education and Action. 2009;3:179-190.

BACKGROUND: The principles of community-based participatory (CBPR) research challenge traditional scientific standards of objectivity and neutrality. Little work has been done to evaluate the quality of data obtained from CBPR studies. OBJECTIVES: We examined factors associated with the completeness and quality of data that participants collected for the Community Health Effects of Industrial Hog Operations (CHEIHO) study, a community-based, participatory, longitudinal, epidemiologic investigation. METHODS: Twice daily for 2 weeks, 101 eastern North Carolina residents collected data on odor from industrialized hog operations, physical health, and mood. Data collected at a single point in time constitute a record. For each record, participant responses were classified as error free or not and missing or not. We used mixed models to quantify associations between errors or missing values and time of day, odor rating, week-in-participation, and presence of a person to assist with data collection. RESULTS: Participants collected data out of order in 2% of 2,949 total records. On average, individual variables were incomplete in 2% of records. Errors and missing data were most common for lung function measurements. Missing data for lung function and blood pressure were less common after the first week of participation (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.20-0.84). Saliva samples were more frequently missing when participants reported odor than when they did not (OR, 1.59; 95% CI, 0.97-2.59). For women, the odds that yes/no variables were missing in week 2 records were higher relative to week 1 (OR, 1.46; 95% CI, 1.01-2.12). CONCLUSIONS: Community members collected relatively complete and consistent data. Better training in use of mechanical devices and more frequent input from researchers could help to improve data quality in CBPR studies.

Wing S, Horton RA, Muhammad N, Grant GR, Tajik M, Thu K. Integrating epidemiology, education, and organizing for environmental justice: Community health effects of industrial hog operations. Am J Public Health. 2008;98:1390-1397.

The environmental justice movement has stimulated community-driven research about the living and working conditions of people of color and low-income communities. We describe an epidemiological study designed to link research with community education and organizing for social justice. In eastern North Carolina, high density industrial swine production occurs in communities of low-income people and people of color. We investigated relationships between the resulting pollution and the health and quality of life of the hog operations’ neighbors. A repeat-measures longitudinal design, community involvement in data collection, and integration of qualitative and quantitative research methods helped promote data quality while providing opportunities for community education and organizing. Research could affect policy through its findings and its mobilization of communities.

Steve Wing/Steve Marshall

Schinasi L, Horton RA, Guidry VT, Wing S , Marshall SW , Morland KB. Air pollution, lung function, and physical symptoms in communities near concentrated swine-feeding operations. Epidemiology, 20:208-15, 2011. BACKGROUND: Concentrated animal feeding operations emit air pollutants that may affect health. We examined associations of reported hog odor and of monitored air pollutants with physical symptoms and lung function in people living within 1.5 miles of hog operations. METHODS: Between September 2003 and September 2005, we measured hydrogen sulfide (H2S), endotoxin, and particulate matter (PM10, PM2.5, and PM2.5-10) for approximately 2-week periods in each of 16 eastern North Carolina communities. During the same time periods, 101 adults sat outside their homes twice a day for 10 minutes, reported hog odor and physical symptoms, and measured their lung function. Conditional fixed-effects logistic and linear regression models were used to derive estimates of associations. RESULTS: The log odds (±1 standard error) of acute eye irritation following 10 minutes outdoors increased by 0.53 (±0.06) for every unit increase in odor, by 0.15 (±0.06) per 1 ppb of H2S, and by 0.36 (±0.11) per 10 μg/m of PM10. Odor and H2S were also associated with irritation and respiratory symptoms in the previous 12 hours. The log odds of difficulty breathing increased by 0.50 (±0.15) per unit of odor. A 10 μg/m increase in mean 12-hour PM2.5 was associated with increased log odds of wheezing (0.84 ± 0.29) and declines in forced expiratory volume in 1 second (-0.04 ± 0.02 L). A 10 EU/mg increase in endotoxin was associated with increased log odds of sore throat (0.10 ± 0.05), chest tightness (0.09 ± 0.04), and nausea (0.10 ± 0.05). CONCLUSIONS: Pollutants measured near hog operations are related to acute physical symptoms in a longitudinal study using analyses that preclude confounding by time-invariant characteristics of individuals.

Wing S, Horton RA, Marshall SW, Thu K, Tajik M, Schinasi L, Schiffman SS. Air pollution and odor in communities near industrial swine operations. Environ Health Perspect. 2008 Oct;116(10):1362-8.

BACKGROUND: Odors can affect health and quality of life. Industrialized animal agriculture creates odorant compounds that are components of a mixture of agents that could trigger symptoms reported by neighbors of livestock operations. OBJECTIVE: We quantified swine odor episodes reported by neighbors and the relationships of these episodes with environmental measurements. METHODS: Between September 2003 and September 2005, 101 nonsmoking volunteers living within 1.5 mi of industrial swine operations in 16 neighborhoods in eastern North Carolina completed twice-daily odor diaries for approximately 2 weeks. Meteorological conditions, hydrogen sulfide, and particulate matter 6.75 miles per hour. The odds of reporting a change in daily activities due to odor increased 62% for each unit increase in average odor during the prior 12 hr (t-value = 7.17). CONCLUSIONS: This study indicates that malodor from swine operations is commonly present in these communities and that the odors reported by neighbors are related to objective environmental measurements and interruption of activities of daily life.

Karin Yeatts

Yeatts K, Svendsen E, Creason J, Alexis N, Herbst M, Scott J, Kupper L, Williams R, Neas L, Cascio W, Devlin RB, Peden DB. Coarse particulate matter (PM2.5-10) affects heart rate variability, blood lipids, and circulating eosinophils in adults with asthma. Environ Health Perspect. 2007 May;115(5):709-14. Epub 2007 Jan 18.

INTRODUCTION: We investigated whether markers of airway and systemic inflammation, as well as heart rate variability (HRV) in asthmatics, change in response to fluctuations in ambient particulate matter (PM) in the coarse [PM with aerodynamic diameter 2.5-10 microm (PM(2.5-10))] and fine (PM(2.5)) size range. METHODS: Twelve adult asthmatics, living within a 30-mile radius of an atmospheric monitoring site in Chapel Hill, North Carolina, were followed over a 12-week period. Daily PM(2.5-10) and PM(2.5) concentrations were measured separately for each 24-hr period. Each subject had nine clinic visits, at which spirometric measures and peripheral blood samples for analysis of lipids, inflammatory cells, and coagulation-associated proteins were obtained. We also assessed HRV [SDNN24HR (standard deviation of all normal-to-normal intervals in a 24-hr recording), ASDNN5 (mean of the standard deviation in all 5-min segments of a 24-hr recording)] with four consecutive 24-hr ambulatory electrocardiogram measurements. Linear mixed models with a spatial covariance matrix structure and a 1-day lag were used to assess potential associations between PM levels and cardiopulmonary end points. RESULTS: For a 1-microg/m(3) increase in coarse PM, SDNN24HR, and ASDNN5 decreased 3.36% (p = 0.02), and 0.77%, (p = 0.05) respectively. With a 1-microg/m(3) increase in coarse PM, circulating eosinophils increased 0.16% (p = 0.01), triglycerides increased 4.8% (p = 0.02), and very low-density lipoprotein increased 1.15% (p = 0.01). No significant associations were found with fine PM, and none with lung function. CONCLUSION: These data suggest that small temporal increases in ambient coarse PM are sufficient to affect important cardiopulmonary and lipid parameters in adults with asthma. Coarse PM may have underappreciated health effects in susceptible populations.

Yeatts K, Sly P, Shore S, Weiss S, Martinez F, Geller A, Bromberg P, Enright P, Koren H, Weissman D, Selgrade M. A brief targeted review of susceptibility factors, environmental exposures, asthma incidence, and recommendations for future asthma incidence research. Environ Health Perspect. 2006 Apr;114(4):634-40.

Relative to research on effects of environmental exposures on exacerbation of existing asthma, little research on incident asthma and environmental exposures has been conducted. However, this research is needed to better devise strategies for the prevention of asthma. The U.S. Environmental Protection Agency (EPA) and National Institute of Environmental Health Sciences held a conference in October 2004 to collaboratively discuss a future research agenda in this area. The first three articles in this mini-monograph summarize the discussion on potential putative environmental exposure; they include an overview of asthma and conclusions of the workshop participants with respect to public health actions that could currently be applied to the problem and research needs to better understand and control the induction and incidence of asthma, the potential role of indoor/outdoor air pollutants in the induction of asthma), and biologics in the induction of asthma. Susceptibility is a key concept in the U.S. EPA “Asthma Research Strategy” document and is associated with the U.S. EPA framework of protecting vulnerable populations from potentially harmful environmental exposures. Genetics, age, and lifestyle (obesity, diet) are major susceptibility factors in the induction of asthma and can interact with environmental exposures either synergistically or antagonistically. Therefore, in this fourth and last article we consider a number of “susceptibility factors” that potentially influence the asthmatic response to environmental exposures and propose a framework for developing research hypotheses regarding the effects of environmental exposures on asthma incidence and induction.


Heaney CD, Wing S , Campbell RL, Caldwell D, Hopkins B, Richardson D , Yeatts K. Relation between malodor, ambient hydrogen sulfide, and health in a community bordering a landfill. Environ Res. 2011 Aug;111(6):847-52. BACKGROUND: Municipal solid waste landfills are sources of air pollution that may affect the health and quality of life of neighboring communities.OBJECTIVES: To investigate health and quality of life concerns of neighbors related to landfill air pollution. METHODS: Landfill neighbors were enrolled and kept twice-daily diaries for 14d about odor intensity, alteration of daily activities, mood states, and irritant and other physical symptoms between January and November 2009. Concurrently, hydrogen sulfide (H(2)S) air measurements were recorded every 15-min. Relationships between H(2)S, odor, and health outcomes were evaluated using conditional fixed effects regression models. RESULTS: Twenty-three participants enrolled and completed 878 twice-daily diary entries. H(2)S measurements were recorded over a period of 80d and 1-h average H(2)S=0.22ppb (SD=0.27; range: 0-2.30ppb). Landfill odor increased 0.63 points (on 5-point Likert-type scale) for every 1ppb increase in hourly average H(2)S when the wind was blowing from the landfill towards the community (95% confidence interval (CI): 0.29, 0.91). Odor was strongly associated with reports of alteration of daily activities (odds ratio (OR)=9.0; 95% CI: 3.5, 23.5), negative mood states (OR=5.2; 95% CI: 2.8, 9.6), mucosal irritation (OR=3.7; 95% CI=2.0, 7.1) and upper respiratory symptoms (OR=3.9; 95% CI: 2.2, 7.0), but not positive mood states (OR=0.6; 95% CI: 0.2, 1.5) and gastrointestinal (GI) symptoms (OR=1.0; 95% CI: 0.4, 2.6). CONCLUSIONS: Results suggest air pollutants from a regional landfill negatively impact the health and quality of life of neighbors.



Learning Objectives

The overall objectives of the program in Environmental and Occupational Epidemiology are to provide an interdisciplinary education that offers the students a solid foundation in environmental and occupational health, with practicum experiences to enhance applied learning, and high-quality research experiences. The learning objectives for the environmental and occupational program area are the same as those for the Department of Epidemiology as a whole with the following additions.

Upon satisfactory completion, students in the program should be able to:

  • Apply the competencies laid out in the Epidemiology Department’s overall learning objectives to the solution of problems in one of more of the program subspecialty areas;
  • Enumerate and discuss important health problems, with their descriptive epidemiology and determinants, for one or more of the program subspecialty areas of environmental/ occupational epidemiology;
  • Identify key surveillance systems and other sources of data relevant to the problem;
  • Discuss study design and measurement issues particular to the subspeciality area;
  • Appreciate key concepts from such related disciplines as environmental sciences, toxicology, and biostatistics;
  • Collaborate with experts in the preceding fields to conduct epidemiologic research;
  • Appreciate the uses of epidemiologic research in identifying hazardous agents, evaluating environmental injustice, and in setting health and safety standards; and
  • Communicate epidemiologic concepts, methods, and findings to community groups, labor unions, health professionals, government agencies, and employers.

In addition, students specializing in occupational or environmental epidemiology who satisfactorily complete the PhD should be able to:

  • Understand the principles of exposure assessment and collaborate with specialists from the relevant fields to assess exposure for epidemiologic research;
  • Analyze and interpret exposure data in epidemiologic studies.


Curriculum and Coursework

Because of the diversity of the subject matter, students and advisors work in consultation to develop individualized programs of study to meet students’ personal objectives. Students will typically specialize in one of the two areas of environmental or occupational epidemiology, but the areas may intersect; for example, the same chemical agent may be present in both workplaces and the ambient environment.


While involvement in research is the primary pathway to developing expertise, formal coursework serves both as a starting point and a means to achieve breadth. The program faculty have adopted curricular guidelines to assist students and their advisors in defining key content areas of this diverse field, designing a program of study, and assuring that key competencies are achieved. Four courses are offered within this program area:

  • Environmental Epidemiology (EPID 785);
  • Occupational Epidemiology (EPID 780);
  • Community-Driven Epidemiology and Environmental Justice (EPID 786); and
  • Integrating Biomarkers in Population-Based Research (EPID 690).

In addition, an Interdisciplinary Approaches in Occupational Health (PUBH 785) course was introduced to provide an interdisciplinary occupational health experience as part of the school’s training.

Epidemiology doctoral students are expected to have an understanding of the major conditions that influence the health of the public, and are strongly encouraged to take substantive epidemiology courses outside their specialty area. Most doctoral students therefore take courses related to major health outcomes, such as Cardiovascular Disease Epidemiology (EPID 735), Advanced Cardiovascular Disease Epidemiology (EPID 737), Cancer Epidemiology and Pathogenesis (EPID 770), Cancer Epidemiology Methods (EPID 771), or Introduction to Methods in Infectious Disease Epidemiology (EPID 752). Many also take Perinatal Epidemiology (EPID 851), Injury as a Public Health Problem (EPID 783), Fundamentals of Public Health Surveillance (EPID 750), or Genetic Epidemiology (EPID 773), or Advanced Genetic Epidemiology (EPID 774). In addition, all students in the Environmental/Occupational Epidemiology Program are advised to take at least two courses outside the Department in areas related to their field of specialization. These are typically in Environmental Sciences and Engineering, but students may choose from a list of courses covering such diverse areas as toxicology, demography, and medical geography.


Students are also encouraged to attend the newly developed Environmental Epidemiology seminar series within our program area as well as the NORA Interdisciplinary Seminar Series offered each year, and other relevant seminars offered by the Department (e.g., cancer, CVD, nutrition, and reproductive epidemiology), the UNC Center for Environmental Health and Susceptibility, the Environmental Protection Agency (EPA), the National Institute of Environmental Health Sciences (NIEHS), Research Triangle International (RTI), and other entities.


Students are strongly encouraged to become involved in research early in their studies. This involvement not only facilitates the student’s intellectual growth as an epidemiologist, but teaches practical skills of data collection, data analysis, and research conduct. Opportunities for research in environmental/occupational epidemiology are available within the Department and the School of Public Health, as well as through other campus or government centers, such as the UNC Center for Environmental Health and Susceptibility, the EPA, and NIEHS.

Participating Faculty

Christy Avery

Christy Avery , Assistant Professor

Research Interests: Air pollution and CVD outcomes

Carri CasteelCarri Casteel

Carri Casteel , Research Assistant Professor

Research Interests: Occupational injury, Occupational Violence

Julie DanielsJulie Daniels

Julie Daniels , Associate Professor

Research Interests: Mercury; Radiation; Perinatal/reproductive outcomes; Neurodevelopmental outcomes

Larry EngelLarry Engel

Larry Engel , Associate Professor

Research Interests: Environmental and occupational exposures; Pesticides; Persistent organic pollutants; Petroleum-related exposures; Cancer, Molecular Epidemiology

Stephanie EngelStephanie Engel

Stephanie Engel , Associate Professor

Research Interests: Environmental Occupational Epidemiology, Child development, Maternal, Reproductive health, Endocrine disruptors, Pesticides, and Molecular epidemiology

Marilie Gammon
Program Lead

Marilie Gammon, Professor

Research Interests: Cancer, Environment (general), Nutrition, Obesity, Women’s health

Steve MarshallSteve Marshall

Stephen Marshall, Professor

Research Interests: Occupational Injury; Survival analysis

Andrew OlshanAndrew Olshan

Andrew Olshan, Professor

Research Interests: Chlorinated by-products; Pesticides; Perinatal/reproductive-related outcomes, Cancer; Molecular epidemiology; Racial disparities

Charles PooleCharles Poole

Charles Poole, Associate Professor

Research Interests: Electromagnetic fields; Pesticides; Cancer; Perinatal/reproductive outcomes; Exposure measurement

David RichardsonDavid Richardson

David Richardson, Associate Professor

Research Interests: Radiation; Occupational exposures; Cancer, Risk modeling

Melissa TroesterMelissa Troester

Melissa Troester, Assistant Professor

Research Interests: Biomarkers of exposure and response; Molecular profiling; Molecular epidemiology; Cancer

Eric WhitselEric Whitsel

Eric Whitsel , Research Assistant Professor

Research Interests: Air pollution; CVD; GIS; Exposure measurement

Steve WingSteve Wing

Steven Wing, Associate Professor

Research Interests: Environmental justice; ionizing radiation; industrial animal production; built environment

Karin B YeattsKarin B Yeatts

Karin Yeatts, Research Assistant Professor

Research Interests: Air pollution; Asthma

Training Grants

Dr. Marilie Gammon directs the Environmental Epidemiology Training Program for the Department of Epidemiology, which is funded by the National Institute of Environmental Health Sciences as a multi-disciplinary training grant to Dr. Amy Herring in the Department of Biostatistics. The Training Program in Environmental Epidemiology offers 6 predoctoral and 3 postdoctoral positions that provide funds to be applied trainee stipends, tuition remission, health insurance, and some travel costs. Application for Training Grant positions is competitive.

Dr. David Richardson directs the Occupational Epidemiology Program for the Department of Epidemiology, which is funded Epidemiology graduate students can also compete for a predoctoral position on the occupational epidemiology training grant, funded by OSHA. Two training grant positions in occupational epidemiology are available. The program is directed by Dr. David Richardson in epidemiology.

Graduate Student Research Assistantships

Research assistantships (RAs) offer students an opportunity to gain research-related experience, develop close working relationships with faculty, and sometimes earn co-authorship on peer-reviewed publications. Information on the type of assistantships available and how to locate them is available from Student Services. A small number of RA positions are typically available in the Environmental/Occupational program. Students interested in an assistantship should submit an application form (available from Student Services), and should discuss this interest with their advisors.

External funding

Students in the Environmental/Occupational Epidemiology training program are sometimes able to secure funding through sources that external to the university. Below is a list of a number of the external sources from which students have received financial support.

National Institute for Environmental Health Sciences Predoctoral Fellowships
Minority Predoctoral Fellowships
National Cancer Institute Summer Program (DCEG)