Lawrence S. Engel

Neurologic Symptoms in Licensed Private Pesticide Applicators in the Agricultural Health Study

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 levels of pesticides. We analyzed cross-sectional data from 18,782 white male licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993–1997. Applicators provided information on lifetime pesticide use and 23 neurologic symptoms typically associated with pesticide intoxication. An indicator of more symptoms (≥10 vs. < 10) during the year before enrollment was associated with cumulative lifetime days of insecticide use: odds ratios (95% confidence intervals) were 1.64 (1.36–1.97) for 1–50 days, 1.89 (1.58–2.25) for 51–500 days, and 2.50 (2.00–3.13) for > 500 days, compared with never users. A modest association for fumigants [> 50 days, 1.50 (1.24–1.81)] and weaker relationships for herbicides [> 500 days, 1.32 (0.99–1.75)] and fungicides [> 50 days, 1.23 (1.00–1.50)] were observed. Pesticide use within the year before enrollment was not associated with symptom count. Only associations with insecticides and fumigants persisted when all four pesticide groups were examined simultaneously. Among chemical classes of insecticides, associations were strongest for organophosphates and organochlorines. Associations with cumulative exposure persisted after excluding individuals who had a history of pesticide poisoning or had experienced an event involving high personal pesticide exposure. These results suggest that self-reported neurologic symptoms are associated with cumulative exposure to moderate levels of fumigants and organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.

Parkinsonism and occupational exposure to pesticides.

OBJECTIVE To examine the risk of parkinsonism related to lifetime occupational exposure to pesticides among a cohort of men, mostly orchardists, in Washington State. METHODS All 310 subjects in this study had previously participated in a cohort study of men occupationally exposed to pesticides. Subjects were given a structured neurological examination and completed a self administered questionnaire which elicited detailed information on pesticide (insecticide, herbicide, and fungicide) use throughout their working careers. Demographic characteristics were also sought. Subjects had a mean age of 69.6 years (range 49–96, SD 8.1). There were 238 (76.8%) subjects who reported some occupational exposure to pesticides, whereas 72 (23.2%) reported none. Parkinsonism was defined by the presence of two or more of rest tremor, rigidity, bradykinesia, and impairment of postural reflexes in subjects not on antiparkinsonian medication, or the presence of at least one sign if they were on such medication. Parkinsons disease was not studied explicitly because of the difficulty in distinguishing it from other parkinsonian syndromes. A generalised linear model was used to estimate prevalence ratios (PRs) for parkinsonism relative to history of farming, pesticide use, and use of well water. RESULTS A PR of 2.0 (95% confidence interval (95% CI) 1.0 to 4.2) was found for subjects in the highest tertile of years of exposure to pesticides; a similarly increased, non-significant, PR was found for the middle tertile (1.9 (95% CI 0.9 to 4.0)), although a trend test did not show a significant exposure-response relation. No increased risks were found associated with specific pesticides or pesticide classes, nor with a history of farming or use of well water. CONCLUSION Parkinsonism may be associated with long term occupational exposure to pesticides, although no associations with specific pesticides could be detected. This finding is consistent with most of the publications on this topic.

Glutathione S-transferase genotypes and stomach cancer in a population-based case-control study in Warsaw, Poland

Glutathione S-transferases are important in the detoxification of a wide range of human carcinogens. Previous studies have shown inconsistent associations between the GSTT1 and GSTM1 null genotypes and stomach cancer risk. We investigated the relationship between these and related genotypes and stomach cancer risk in a population-based case-control study in Warsaw, Poland, where stomach cancer incidence and mortality rates are among the highest in Europe. DNA from blood samples was available for 304 stomach cancer patients and 427 control subjects. We observed a 1.48-fold increased risk for stomach cancer (95% confidence interval 0.97-2.25) in patients with the GSTT1 null genotype but no evidence of increased risk associated with the GSTM1, GSTM3 or GSTP1 genotypes. Furthermore, the stomach cancer risk associated with the GSTT1 null genotype varied by age at diagnosis, with odds ratios of 3.85, 1.91, 1.78 and 0.59 for those diagnosed at ages less than 50, 50-59, 60-69 and 70 years or older, respectively (P trend = 0.01). This was due to a shift in the GSTT1 genotype distribution across age groups among stomach cancer patients only. These results suggest that the GSTT1 null genotype may be associated with increased risk of stomach cancer.

Neurophysiological Function in Farm Workers Exposed to Organophosphate Pesticides

To investigate neurophysiological effects of low-level exposure to foliar organophosphate residues during one season among agricultural workers, the authors performed a cross-sectional study of 67 Hispanic farm workers and 68 age-, gender-, ethnicity-, and education-matched reference subjects. The neurophysiological examination included sensory and motor nerve conduction and neuromuscular junction testing. Erythrocyte cholinesterase activity was measured at the time of examination. No statistically significant neurophysiological differences between the exposed and reference groups were observed. Farm workers and reference subjects had similar sensory nerve latency and amplitude (sural), motor nerve conduction velocity (ulnar), and neuromuscular junction function (ulnar). No relationship between duration of exposure during the season and electrophysiological measures of nerve function was found. Exposure of farm workers to the low levels of organophosphate pesticides during one season experienced by farm workers in this study was not associated with impaired peripheral neurophysiological function.

Prediagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors

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 (ORT3) 2.2; 95% CI, 0.7–6.5; pWilcoxon = 0.07), oxychlordane (ORT3 3.2; 95% CI, 0.6–16.8; pWilcoxon = 0.05), trans-nonachlor (ORT3 2.6; 95% CI, 0.7–8.9; pWilcoxon = 0.07), and total chlordanes (ORT3 2.0; 95% CI, 0.6–7.2; pWilcoxon = 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.

Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of Shanghai women and men.

Background: Exposure to certain phenols is ubiquitous because of their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations. Objectives: We sought to identify predictors of exposure and to assess the reproducibility of phenol concentrations across serial spot urine samples among Chinese adults. Methods: We measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected during 1997–2006 from 50 participants of the Shanghai Women’s Health Study cohort and during 2002–2006 from 50 participants of the Shanghai Men’s Health Study cohort. We investigated predictors of concentrations using the Satterthwaite t-test, and assessed reproducibility among serial samples using intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs). Results: Creatinine-corrected phenol concentrations were generally higher among women than men. Participants who had taken medicine within the previous 24 hr had higher concentrations of propyl paraben. Cigarette smoking was associated with lower concentrations of propyl and methyl parabens among men. Bottled water consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5-dichlorophenol concentrations among women. Among men, reproducibility across serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC = 0.54–0.60, SCC = 0.43–0.56), but lower for other analytes (ICC = 0.20–0.29). Reproducibility among women was low (ICC = 0.13–0.39), but increased when restricted to morning-only urine samples. Conclusions: Among these 100 Shanghai residents, urinary phenol concentrations varied by sex, smoking, and consumption of bottled water. Our results suggest that a single urine sample may be adequate for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5-dichlorophenol among men and, under certain circumstances, among women. Citation: Engel LS, Buckley JP, Yang G, Liao LM, Satagopan J, Calafat AM, Matthews CE, Cai Q, Ji BT, Cai H, Engel SM, Wolff MS, Rothman N, Zheng W, Xiang YB, Shu XO, Gao YT, Chow WH. 2014. Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of Shanghai women and men. Environ Health Perspect 122:733–740; http://dx.doi.org/10.1289/ehp.1306830

Validity study of self-reported pesticide exposure among orchardists.

Self-reported work histories are often the only means of estimating occupational exposures in epidemiologic research. The objective of this study was to examine the accuracy of recall of historical pesticide use among orchardists. All 185 orchardists in this study had participated previously in a cohort study of men occupationally exposed to pesticides. In that study (1972 to 1976), subjects were interviewed annually and asked to list pesticides used since the last interview. In 1997, 265 of the 440 presumed-living orchardists from the original cohort were successfully recontacted and asked to complete a detailed questionnaire concerning their lifetime use of pesticides; 185 (69.8% of farmers successfully contacted) agreed. Considering the 1972–1976 data as the standard, sensitivity and specificity of recall were calculated for certain pesticides and pesticide categories. Sensitivity of recall was good to excellent (0.6–0.9) for the broad categories of insecticides, herbicides, and fungicides, for heavily used chemical classes, such as organophosphates and organochlorines, and for commonly used pesticides; it was lower and more variable (0.1–0.6) for specific pesticides. Recall specificity was greatest (0.7–0.9) for the least used pesticides and chemical classes, such as dithiocarbamates and manganese-containing pesticides, and was generally modest for the rest (0.5–0.6). There was no evidence of selection bias between study participants and nonparticipants. In conclusion, recall accuracy was good for commonly used pesticides and pesticide categories. This level of recall accuracy is probably adequate for epidemiologic analyses of broad categories of pesticides, but is a limitation for detecting more specific associations.

Prevalence of exposure to solvents, metals, grain dust, and other hazards among farmers in the Agricultural Health Study.

Exposures to multiple chemical, physical, and biological agents in agricultural work environments can result in confounding that may obscure or distort risks observed in epidemiologic studies. The Agricultural Health Study (AHS) is a large epidemiology study being conducted to investigate health risks among pesticide applicators and their families. During enrollment in the AHS, questionnaires were administered to over 52,000 licensed pesticide applicators from North Carolina and Iowa, who were mostly farmers. Questions about the frequency of various farming tasks were used to estimate the prevalence of exposure to solvents (25%), metals (68%), grain dusts (65%), diesel exhaust fumes (93%), and other hazards, including exposure to pesticides. Most of the farmers in the AHS reported performing routine maintenance tasks at least once a month, such as painting (63%), welding (64%), and repair of pesticide equipment (58%). The majority of farmers (74% in North Carolina; 59% in Iowa) reported holding nonfarm jobs, of which the most frequent were construction and transportation. The majority of the farmers enrolled in the AHS (55%) also reported that they mixed or applied pesticides on 10 or more days per year. The associations between the use of pesticides and the frequency with which the farmers in the AHS reported performing various types of specific farming activities were assessed to evaluate potential confounding. Confounding risk ratios calculated for these activities suggest that the magnitude of bias due to confounding is likely to be minimal.

Polychlorinated Biphenyls and Non-Hodgkin Lymphoma

Several epidemiologic studies suggest that polychlorinated biphenyl (PCB) levels measured in peripheral blood or adipose tissue are related to increased risk of non-Hodgkin lymphoma (NHL) and, therefore, may be at least partially responsible for the rising incidence of NHL unrelated to HIV infection in recent decades. Case-control studies that measured PCBs in blood, adipose tissue, or household carpet dust, at the time of diagnosis, have observed elevated NHL risk associated with concentrations of either total PCBs or of specific congeners. Similar associations have been found in a number of prospective cohorts. These associations do not seem to be due to confounding by other organochlorines or by other known NHL risk factors. These results support evidence of PCB carcinogenicity from animal studies. However, interpretation of the epidemiologic evidence is limited by the wide range in measurement precision across congeners and by the moderate to high correlation among many congeners. Occupational cohort studies provide very limited support for a relationship between PCBs and NHL. In conclusion, there is mounting evidence of a relationship between certain PCBs and risk of NHL, but important questions remain, especially regarding the magnitude, timing, and causality of that relationship. (Cancer Epidemiol Biomarkers Prev 2007;16(3):373–6)

Vehicular Traffic-Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP).

Background Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure. Objectives Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence. Methods Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression. Results The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants]. Conclusions In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise. Citation Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.1307736