Residential Pesticides and Childhood Leukemia: A Systematic Review and Meta-Analysis

Objective

We conducted a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia.

Data sources

Searches of MEDLINE and other electronic databases were performed (1950–2009). Reports were included if they were original epidemiologic studies of childhood leukemia, followed a case–control or cohort design, and assessed at least one index of residential/household pesticide exposure/use. No language criteria were applied.

Data extraction

Study selection, data abstraction, and quality assessment were performed by two independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs).

Data synthesis

Of the 17 identified studies, 15 were included in the meta-analysis. Exposures during pregnancy to unspecified residential pesticides (summary OR = 1.54; 95% CI, 1.13–2.11; I² = 66%), insecticides (OR = 2.05; 95% CI, 1.80–2.32; I² = 0%), and herbicides (OR = 1.61; 95% CI, 1.20–2.16; I² = 0%) were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides (OR = 1.38; 95% CI, 1.12–1.70; I² = 4%) and insecticides (OR = 1.61; 95% CI, 1.33–1.95; I² = 0%) were also positively associated with childhood leukemia, but there was no association with herbicides.

Conclusions

Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure–response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.     

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease

Background

Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson’s disease (PD) risk.

Materials

Methods: In 324 incident PD patients and 334 population controls from our rural California case–control study, we genotyped rs2652510, rs2550956 (for the DAT 5′ clades), and the 3′ variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele–pesticide interactions.

Results

PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08–2.57] and 3′ VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96–3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88–10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70–12.1). We obtained similar results for occupational pesticide measures.

Discussion

Using two independent pesticide measures, we a) replicated previously reported gene–environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.

Conclusion

Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk.     

Household Exposure to Paint and Petroleum Solvents,Chromosomal Translocations,and the Risk of Childhood Leukemia

Background

Few studies have examined the association between home use of solvents and paint and the risk of childhood leukemia.

Objectives

In this case–control study, we examined whether the use of paint and petroleum solvents at home before birth and in early childhood influenced the risk of leukemia in children.

Methods

We based our analyses on 550 cases of acute lymphoblastic leukemia (ALL), 100 cases of acute myeloid leukemia (AML), and one or two controls per case individually matched for sex, age, Hispanic status, and race. We conducted further analyses by cytogenetic subtype. We used conditional logistic regression techniques to adjust for income.

Results

ALL risk was significantly associated with paint exposure [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.26–2.15], with a higher risk observed when paint was used postnatally, by a person other than the mother, or frequently. The association was restricted to leukemia with translocations between chromosomes 12 and 21 (OR = 4.16; 95% CI, 1.66–10.4). We found no significant association between solvent use and ALL risk overall (OR = 1.15; 95% CI, 0.87–1.51) or for various cytogenetic subtypes, but we observed a significant association in the 2.0- to 5.9-year age group (OR = 1.55; 95% CI, 1.07–2.25). In contrast, a significant increased risk for AML was associated with solvent (OR = 2.54; 95% CI, 1.19–5.42) but not with paint exposure (OR = 0.64; 95% CI, 0.32–1.25).

Conclusions

The association of ALL risk with paint exposure was strong, consistent with a causal relationship, but further studies are needed to confirm the association of ALL and AML risk with solvent exposure.     

Depression and Pesticide Exposures among Private Pesticide Applicators Enrolled in the Agricultural Health Study

Background

We evaluated the relationship between diagnosed depression and pesticide exposure using information from private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997 in Iowa and North Carolina.

Methods

There were 534 cases who self-reported a physician-diagnosed depression and 17,051 controls who reported never having been diagnosed with depression and did not feel depressed more than once a week in the past year. Lifetime pesticide exposure was categorized in three mutually exclusive groups: low (< 226 days, the reference group), intermediate (226–752 days), and high (> 752 days). Two additional measures represented acute high-intensity pesticide exposures: an unusually high pesticide exposure event (HPEE) and physician-diagnosed pesticide poisoning. Logistic regression analyses were performed relating pesticide exposure to depression.

Results

After adjusting for state, age, education, marital status, doctor visits, alcohol use, smoking, solvent exposure, not currently having crops or animals, and ever working a job off the farm, pesticide poisoning was more strongly associated with depression [odds ratio (OR) = 2.57; 95% confidence interval (CI), 1.74–3.79] than intermediate (OR = 1.07; 95% CI, 0.87–1.31) or high (OR = 1.11; 95% CI, 0.87–1.42) cumulative exposure or an HPEE (OR = 1.65; 95% CI, 1.33–2.05). In analysis of a subgroup without a history of acute poisoning, high cumulative exposure was significantly associated with depression (OR = 1.54; 95% CI, 1.16–2.04).

Conclusion

These findings suggest that both acute high-intensity and cumulative pesticide exposure may contribute to depression in pesticide applicators. Our study is unique in reporting that depression is also associated with chronic pesticide exposure in the absence of a physician-diagnosed poisoning.     

Pesticide Use and Cutaneous Melanoma in Pesticide Applicators in the Agricultural Heath Study

Background

Melanoma rates continue to increase; however, few risk factors other than sun sensitivity and ultraviolet radiation (including sun exposure) have been identified. Although studies of farmers have shown an excess risk of melanoma and other skin cancers, it is unclear how much of this is related to sun exposure compared with other agricultural exposures.

Methods

We examined dose–response relationships for 50 agricultural pesticides and cutaneous melanoma incidence in the Agricultural Health Study cohort of licensed pesticide applicators, along with ever use of older pesticides that contain arsenic. Logistic regression was used to examine odds ratios (ORs) and 95% confidence intervals (CIs) associated with pesticide exposure adjusted for age, sex, and other potential confounders.

Results

We found significant associations between cutaneous melanoma and maneb/mancozeb (63 exposure days: OR = 2.4; 95% CI, 1.2–4.9; trend p = 0.006), parathion (≥ 56 exposure days: OR = 2.4; 95% CI, 1.3–4.4; trend p = 0.003), and carbaryl (≥ 56 exposure days: OR = 1.7; 95% CI, 1.1–2.5; trend p = 0.013). Other associations with benomyl and ever use of arsenical pesticides were also suggested.

Conclusions

Most previous melanoma literature has focused on host factors and sun exposure. Our research shows an association between several pesticides and melanoma, providing support for the hypotheses that agricultural chemicals may be another important source of melanoma risk.     

Parental Exposure to Pesticides and Childhood Brain Cancer: U.S. Atlantic Coast Childhood Brain Cancer Study

Background

The etiology of childhood brain cancer remains largely unknown. However, previous studies have yielded suggestive associations with parental pesticide use.

Objectives

We aimed to evaluate parental exposure to pesticides at home and on the job in relation to the occurrence of brain cancer in children.

Methods

We included 526 one-to-one–matched case–control pairs. Brain cancer cases were diagnosed at < 10 years of age, and were identified from statewide cancer registries of four U.S. Atlantic Coast states. We selected controls by random digit dialing. We conducted computer-assisted telephone interviews with mothers. Using information on residential pesticide use and jobs held by fathers during the 2-year period before the child’s birth, we assessed potential exposure to insecticides, herbicides, and fungicides. For each job, two raters independently classified the probability and intensity of exposure; 421 pairs were available for final analysis. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, after adjustment for maternal education.

Results

A significant risk of astrocytoma was associated with exposures to herbicides from residential use (OR = 1.9; 95% CI, 1.2–3.0). Combining parental exposures to herbicides from both residential and occupational sources, the elevated risk remained significant (OR = 1.8; 95% CI, 1.1–3.1). We observed little association with primitive neuroectodermal tumors (PNET) for any of the pesticide classes or exposure sources considered.

Conclusions

Our observation is consistent with a previous literature reporting suggestive associations between parental exposure to pesticides and risk of astrocytoma in offspring but not PNET. However, these findings should be viewed in light of limitations in exposure assessment and effective sample size.     

Pesticide Exposure and Hypertensive Disorders During Pregnancy

Background

Hypertensive disorders of pregnancy, including pregnancy-induced hypertension (PIH) and preeclampsia (PE), complicate 2–8% of pregnancies. Few studies have examined environmental risk factors in relation to these conditions.

Objectives

Our goal was to examine whether pesticide exposure during pregnancy was associated with hypertensive disorders of pregnancy.

Methods

We analyzed self-reported data from 11,274 wives of farmers enrolled in the Agricultural Health Study (AHS) between 1993 and 1997. Using logistic regression models, we estimated the adjusted odds ratios (AORs) for PIH and PE associated with pesticide-related activities during the first trimester of pregnancy.

Results

First-trimester residential and agricultural activities with potential exposure to pesticides were associated with both PIH [residential AOR = 1.27; 95% confidence interval (CI), 1.02–1.60; agricultural AOR = 1.60; 95% CI, 1.05–2.45] and PE (residential AOR = 1.32; 95% CI, 1.02–1.70; agricultural AOR = 2.07; 95% CI, 1.34–3.21).

Conclusions

Exposure to pesticides during pregnancy may increase the risk of hypertensive disorders of pregnancy. Laboratory research may provide insights into relationships between pesticide exposure and hypertensive diseases of pregnancy.     

Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver Cirrhosis in The Gambia,West Africa

Background

Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region.

Objectives

We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in The Gambia.

Methods

Ninety-seven individuals were diagnosed with cirrhosis using a validated ultrasound scoring system and were compared with 397 controls. Participants reported demographic and food frequency information. Blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, HCV RNA, and the aflatoxin-associated 249^ser TP53 mutation.

Results

HBsAg seropositivity was associated with a significant increase in risk of cirrhosis [odds ratio (OR) = 8.0; 95% confidence interval (CI), 4.4–14.7] as was the presence of HBeAg (OR = 10.3; 95% CI, 2.0–53.9) and HCV infection (OR = 3.3; 95% CI, 1.2–9.5). We present novel data that exposure to aflatoxin, as assessed both by high lifetime groundnut (peanut) intake and by the presence of the 249^ser TP53 mutation in plasma, is associated with a significant increase in the risk for cirrhosis (OR = 2.8; 95% CI, 1.1–7.7 and OR = 3.8; 95% CI, 1.5–9.6, respectively). Additionally, aflatoxin and hepatitis B virus exposure appeared to interact synergistically to substantially increase the risk of cirrhosis, although this was not statistically significant.

Conclusions

Our results suggest that the spectrum of morbidity associated with aflatoxin exposure could include cirrhosis.     

Lung Cancer in Chinese Women: Evidence for an Interaction between Tobacco Smoking and Exposure to Inhalants in the Indoor Environment

Background

Epidemiologic data suggest that Chinese women have a high incidence of lung cancer in relation to their smoking prevalence. In addition to active tobacco smoke exposure, other sources of fumes and airborne particles in the indoor environment, such as cooking and burning of incense and mosquito coils, have been considered potential risk factors for lung cancer.

Objectives

We used a case–control study to explore effects of inhalants from combustion sources common in the domestic environment on lung cancer and their modification by active tobacco smoking.

Methods

We analyzed 703 primary lung cancer cases and 1,578 controls. Data on demographic background and relevant exposures were obtained by face-to-face interviews in the hospital.

Results

We observed a positive relationship with daily exposure to incense or mosquito coils and to cooking fumes only among smokers, and no association among lifetime nonsmokers. Interactions between smoking and frequency of cooking, or exposure to incense or mosquito coils were statistically significant and consistent with synergistic effects on lung cancer. The odds ratio (OR) comparing smokers without daily incense or mosquito coil exposure with nonsmokers without daily exposure was 2.80 [95% confidence interval (CI), 1.86–4.21], whereas the OR comparing smokers with daily exposure to the same referent group was 4.61 (95% CI, 3.41–6.24). In contrast, daily exposure to incense or mosquito coils was not associated with lung cancer among nonsmokers (OR = 0.91; 95% CI, 0.72–1.16). We observed the same pattern of associations for smokers without (OR = 2.31; 95% CI, 1.52–3.51) and with (OR = 4.50; 95% CI, 3.21–6.30) daily cooking exposure compared with nonsmokers, with no evidence of an association with daily cooking exposure among nonsmokers.

Conclusion

Our results suggest that active tobacco smoking not only is an important risk factor for development of lung cancer, but also may cause smokers to be more susceptible to the risk-enhancing effects of other inhalants.     

Non–Dioxin-Like Polychlorinated Biphenyls and Risk of Endometriosis

Background

Endometriosis, a gynecologic disorder affecting 8–10% of reproductive-age women in the United States, is defined as the presence of endometrial tissue outside the uterus and is linked to pelvic pain and infertility. Environmental contaminants, including polychlorinated biphenyls (PCBs), are hypothesized to contribute to endometriosis risk through effects on steroid hormones.

Objective

We evaluated serum concentrations of certain noncoplanar PCBs, which have no or only weak dioxin-like properties, as risk factors for endometriosis.

Methods

In a case–control study of Group Health enrollees in western Washington State, 20 PCB congeners were measured in serum from surgically confirmed endometriosis cases that were newly diagnosed between 1996 and 2001 (n = 251) and from female controls matched for age and reference year (n = 538).

Results

Summed and estrogenic PCB concentrations were not associated with endometriosis risk [summed: odds ratio (OR) = 1.3; 95% confidence interval (CI), 0.8–2.2; estrogenic: OR = 1.1; 95% CI, 0.8–1.4]. Although several congener-specific ORs were statistically above or below the null (PCB 170: third quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.9; PCB 196: third quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7; PCB 201: second vs. lowest: OR = 0.5; 95% CI, 0.3–0.8; third quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7), there were no overall consistent patterns of endometriosis risk.

Conclusions

Taken in context with other North American studies, our findings suggest that noncoplanar PCB concentrations consistent within the range of exposure currently observed in western Washington State do not contribute meaningfully to endometriosis risk.     

Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study

Background

Permethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens.

Objective

In this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS).

Methods

A total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993–1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure.

Results

We found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76–11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41–10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups.

Conclusions

This study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation.     

S-Ethyl-N,N-dipropylthiocarbamate Exposure and Cancer Incidence among Male Pesticide Applicators in the Agricultural Health Study: A Prospective Cohort

Background

The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled between 1993 and 1997. EPTC (S-ethyl-N,N-dipropylthiocarbamate) is a thiocarbamate herbicide used in every region of the United States. The U.S. Environmental Protection Agency reports that EPTC is most likely not a human carcinogen; however, the previous epidemiologic data on EPTC exposure and cancer risk were limited.

Objectives

The purpose of this study was to examine cancer incidence and EPTC use in 48,378 male pesticide applicators enrolled in the AHS.

Methods

We estimated the rate ratio (RR) and 95% confidence intervals (CIs) for all cancers and selected cancer sites using Poisson regression. We assessed EPTC exposure using two quantitative metrics: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that accounts for application factors that modify personal exposure likelihood.

Results

Among the 9,878 applicators exposed to EPTC, 470 incident cancer cases were diagnosed during the follow-up period ending December 2004 compared with the 1,824 cases among individuals reporting no use. Although EPTC was associated with colon cancer in the highest tertile of both lifetime exposure days and intensity-weighted lifetime days (RR = 2.09; 95% CI, 1.26–3.47 and RR = 2.05; 95% CI, 1.34–3.14, respectively) and the trend test was < 0.01 for both, the pattern of RR was not monotonic with increasing use. There was a suggestion of an association with leukemia. No other associations were observed.

Conclusion

In this analysis, EPTC use appeared to be associated with colon cancer and leukemia. However, given the relatively small number of cases in the highest exposure tertile, results should be interpreted with caution, and further investigations are needed.     

Childhood Lymphohematopoietic Cancer Incidence and Hazardous Air Pollutants in Southeast Texas, 1995–2004

Background

Cancer is the second leading cause of death among U.S. children with few known risk factors. There is increasing interest in the role of air pollutants, including benzene and 1,3-butadiene, in the etiology of childhood cancers.

Objective

Our goal was to assess whether census tracts with the highest benzene or 1,3-butadiene ambient air levels have increased childhood lymphohematopoietic cancer incidence.

Methods

Our ecologic analysis included 977 cases of childhood lymphohematopoietic cancer diagnosed from 1995–2004. We obtained the U.S. Environmental Protection Agency’s 1999 modeled estimates of benzene and 1,3-butadiene for 886 census tracts surrounding Houston, Texas. We ran Poisson regression models by pollutant to explore the associations between pollutant levels and census-tract cancer rates. We adjusted models for age, sex, race/ethnicity, and community-level socioeconomic status (cSES).

Results

Census tracts with the highest benzene levels had elevated rates of all leukemia [rate ratio (RR) = 1.37; 95% confidence interval (CI), 1.05, 1.78]. This association was higher for acute myeloid leukemia (AML) (RR = 2.02; 95% CI, 1.03–3.96) than for acute lymphocytic leukemia (ALL) (RR = 1.24; 95% CI, 0.92–1.66). Among census tracts with the highest 1,3-butadiene levels, we observed RRs of 1.40 (95% CI, 1.07–1.81), 1.68 (95% CI, 0.84–3.35), and 1.32 (95% CI, 0.98–1.77) for all leukemia, AML, and ALL, respectively. We detected no associations between benzene or 1,3-butadiene levels and lymphoma incidence. Results that examined joint exposure to benzene and 1,3-butadiene were similar to those that examined each pollutant separately.

Conclusions

Our ecologic analysis suggests an association between childhood leukemia and hazardous air pollution; further research using more sophisticated methodology is warranted.     

Association between Local Traffic-Generated Air Pollution and Preeclampsia and Preterm Delivery in the South Coast Air Basin of California

Background

Preeclampsia is a major complication of pregnancy that can lead to substantial maternal and perinatal morbidity, mortality, and preterm birth. Increasing evidence suggests that air pollution adversely affects pregnancy outcomes. Yet few studies have examined how local traffic-generated emissions affect preeclampsia in addition to preterm birth.

Objectives

We examined effects of residential exposure to local traffic-generated air pollution on preeclampsia and preterm delivery (PTD).

Methods

We identified 81,186 singleton birth records from four hospitals (1997–2006) in Los Angeles and Orange Counties, California (USA). We used a line-source dispersion model (CALINE4) to estimate individual exposure to local traffic-generated nitrogen oxides (NO_x) and particulate matter < 2.5 μm in aerodynamic diameter (PM_2.5) across the entire pregnancy. We used logistic regression to estimate effects of air pollution exposures on preeclampsia, PTD (gestational age < 37 weeks), moderate PTD (MPTD; gestational age < 35 weeks), and very PTD (VPTD; gestational age < 30 weeks).

Results

We observed elevated risks for preeclampsia and preterm birth from maternal exposure to local traffic-generated NO_x and PM_2.5. The risk of preeclampsia increased 33% [odds ratio (OR) = 1.33; 95% confidence interval (CI), 1.18–1.49] and 42% (OR = 1.42; 95% CI, 1.26–1.59) for the highest NO_x and PM_2.5 exposure quartiles, respectively. The risk of VPTD increased 128% (OR = 2.28; 95% CI, 2.15–2.42) and 81% (OR = 1.81; 95% CI, 1.71–1.92) for women in the highest NO_x and PM_2.5 exposure quartiles, respectively.

Conclusion

Exposure to local traffic-generated air pollution during pregnancy increases the risk of preeclampsia and preterm birth in Southern California women. These results provide further evidence that air pollution is associated with adverse reproductive outcomes.     

Residential Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Childhood Leukemia

Background

Incidence of childhood leukemia in industrialized countries rose significantly during 1975–2004, and the reasons for the increase are not understood.

Objectives

We used carpet dust as an exposure indicator to examine the risk of childhood leukemia in relation to residential exposure to persistent organochlorine chemicals: six polychlorinated biphenyl (PCB) congeners and the pesticides α- and γ-chlordane, p,p′-DDT (dichlorodiphenyltrichloroethane), p,p′-DDE (dichlorodiphenyldichloroethylene), methoxychlor, and pentachlorophenol.

Methods

We conducted a population-based case–control study in 35 counties in northern and central California in 2001–2006. The study included 184 acute lymphocytic leukemia (ALL) cases 0–7 years of age and 212 birth certificate controls matched to cases by birth date, sex, race, and Hispanic ethnicity. We collected carpet dust samples from the room where the child spent the most time before diagnosis (similar date for controls) using a specialized vacuum.

Results

Detection of any PCB congener in the dust conferred a 2-fold increased risk of ALL [odds ratio (OR) = 1.97; 95% confidence interval (CI), 1.22–3.17]. Compared with those in the lowest quartile of total PCBs, the highest quartile was associated with about a 3-fold risk (OR = 2.78; 95% CI, 1.41–5.48), and the positive trend was significant (p = 0.017). Significant positive trends in ALL risk were apparent with increasing concentrations of PCB congeners 118, 138, and 153. We observed no significant positive associations for chlordane, DDT, DDE, methoxychlor, or pentachlorophenol. The associations with PCBs were stronger among non-Hispanic whites than among Hispanics despite similar distributions of PCB levels among controls in each racial/ethnic group.

Conclusions

Our findings suggest that PCBs, which are considered probable human carcinogens and cause perturbations of the immune system, may represent a previously unrecognized risk factor for childhood leukemia.     

A case-control study of occupational exposure to trichloroethylene and non-Hodgkin lymphoma

Background

Previous epidemiologic findings suggest an association between exposure to trichloroethylene (TCE), a chlorinated solvent primarily used for vapor degreasing of metal parts, and non-Hodgkin lymphoma (NHL).

Objectives

We investigated the association between occupational TCE exposure and NHL within a population-based case–control study using detailed exposure assessment methods.

Methods

Cases (n = 1,189; 76% participation rate) and controls (n = 982; 52% participation rate) provided information on their occupational histories and, for selected occupations, on possible workplace exposure to TCE using job-specific interview modules. An industrial hygienist assessed potential TCE exposure based on this information and a review of the TCE industrial hygiene literature. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating NHL and different metrics of estimated TCE exposure, categorized using tertiles among exposed controls, with unexposed subjects as the reference group.

Results

We observed associations with NHL for the highest tertiles of estimated average weekly exposure (23 exposed cases; OR = 2.5; 95% CI, 1.1–6.1) and cumulative exposure (24 exposed cases; OR = 2.3; 95% CI, 1.0–5.0) to TCE. Tests for trend with these metrics surpassed or approached statistical significance (p-value for trend = 0.02 and 0.08, respectively); however, we did not observe dose–response relationships across the exposure levels. Overall, neither duration nor intensity of exposure was associated with NHL, although we observed an association with the lowest tertile of exposure duration (OR = 2.1; 95% CI, 1.0–4.7).

Conclusions

Our findings offer additional support for an association between high levels of exposure to TCE and increased risk of NHL. However, we cannot rule out the possibility of confounding from other chlorinated solvents used for vapor degreasing and note that our exposure assessment methods have not been validated.     

Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age

Background

Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting.

Objective

We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis.

Methods

We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs.

Results

We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs.

Conclusions

The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis.     

Lung Cancer in a U.S. Population with Low to Moderate Arsenic Exposure

Background

Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 μg/L) in drinking water.

Objectives

We examined associations between arsenic and lung cancer.

Methods

A population-based case–control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled–plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level).

Results

Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00–7.57] for toenail arsenic concentration ≥ 0.114 μg/g, versus < 0.05 μg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39–5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic ≥ 0.05 μg/g (OR = 4.78; 95% CI, 1.87–12.2) than among individuals with low toenail arsenic and no history of lung disease.

Conclusion

Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies.     

Exposure to Polyfluoroalkyl Chemicals and Attention Deficit/Hyperactivity Disorder in U.S. Children 12–15 Years of Age

Background

Polyfluoroalkyl chemicals (PFCs) have been widely used in consumer products. Exposures in the United States and in world populations are widespread. PFC exposures have been linked to various health impacts, and data in animals suggest that PFCs may be potential developmental neurotoxicants.

Objectives

We evaluated the associations between exposures to four PFCs and parental report of diagnosis of attention deficit/hyperactivity disorder (ADHD).

Methods

Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and 2003–2004 for children 12–15 years of age. Parental report of a previous diagnosis by a doctor or health care professional of ADHD in the child was the primary outcome measure. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) levels were measured in serum samples from each child.

Results

Parents reported that 48 of 571 children included in the analysis had been diagnosed with ADHD. The adjusted odds ratio (OR) for parentally reported ADHD in association with a 1-μg/L increase in serum PFOS (modeled as a continuous predictor) was 1.03 [95% confidence interval (CI), 1.01–1.05]. Adjusted ORs for 1-μg/L increases in PFOA and PFHxS were also statistically significant (PFOA: OR = 1.12; 95% CI, 1.01–1.23; PFHxS: OR = 1.06; 95% CI, 1.02–1.11), and we observed a nonsignificant positive association with PFNA (OR = 1.32; 95% CI, 0.86–2.02).

Conclusions

Our results, using cross-sectional data, are consistent with increased odds of ADHD in children with higher serum PFC levels. Given the extremely prevalent exposure to PFCs, follow-up of these data with cohort studies is needed.     

Benzene Exposure Near the U.S. Permissible Limit Is Associated with Sperm Aneuploidy

Background

Benzene is a common industrial chemical known to induce leukemia and other blood disorders, as well as aneuploidy, in both human blood cells and sperm at exposures > 10 ppm. Recent reports have identified health effects at exposure levels < 1 ppm, the permissible exposure limit (PEL; 8 hr) set by the U.S. Occupational Safety and Health Administration.

Objective

We investigated whether occupational exposures to benzene near 1 ppm induce aneuploidy in sperm.

Methods

We used multicolor fluorescence in situ hybridization to measure the incidence of sperm with numerical abnormalities of chromosomes X, Y, and 21 among 33 benzene-exposed men and 33 unexposed men from Chinese factories. Individual exposures were assessed using personal air monitoring and urinary concentrations of benzene and trans,trans-muconic acid (E,E-MA). Air benzene concentrations were not detectable in unexposed men; in exposed men, concentrations ranged from below the detection limit to 24 ppm (median, 2.9 ppm), with 27% of exposed men (n = 9) having concentrations of ≤ 1 ppm. Exposed men were categorized into low and high groups based on urinary E,E-MA (median concentrations of 1.9 and 14.4 mg/L, respectively; median air benzene of 1 and 7.7 ppm, respectively), and aneuploidy frequencies were compared with those of unexposed men.

Results

Sperm aneuploidy increased across low- and high-exposed groups for disomy X [incidence rate ratio (IRR) = 2.0; 95% confidence interval (CI), 1.1–3.4; and IRR = 2.8; 95% CI, 1.5–4.9, respectively], and for overall hyperhaploidy for the three chromosomes investigated (IRR = 1.6; 95% CI, 1.0–2.4; and IRR = 2.3; 95% CI, 1.5–3.6, respectively). We also found elevated disomy X and hyperhaploidy in the nine men exposed to ≤ 1 ppm benzene compared with unexposed men (IRR = 1.8; 95% CI, 1.1–3.0; and IRR = 2.0; 95% CI, 1.1–3.9, respectively).

Conclusions

Benzene appeared to increase the frequencies of aneuploid sperm for chromosomes associated with chromosomal abnormality syndromes in human offspring, even in men whose air benzene exposure was at or below the U.S. permissible exposure limit.