Do Perfluoroalkyl Compounds Impair Human Semen Quality?

Background

Perfluoroalkyl acids (PFAAs) are found globally in wildlife and humans and are suspected to act as endocrine disruptors. There are no previous reports of PFAA levels in adult men from Denmark or of a possible association between semen quality and PFAA exposure.

Objectives

We investigated possible associations between PFAAs and testicular function. We hypothesized that higher PFAA levels would be associated with lower semen quality and lower testosterone levels.

Methods

We analyzed serum samples for levels of 10 different PFAAs and reproductive hormones and assessed semen quality in 105 Danish men from the general population (median age, 19 years).

Results

Considerable levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid were found in all young men (medians of 24.5, 4.9, and 6.6 ng/mL, respectively). Men with high combined levels of PFOS and PFOA had a median of 6.2 million normal spermatozoa in their ejaculate in contrast to 15.5 million among men with low PFOS–PFOA (p = 0.030). In addition, we found nonsignificant trends with regard to lower sperm concentration, lower total sperm counts, and altered pituitary–gonadal hormones among men with high PFOS–PFOA levels.

Conclusion

High PFAA levels were associated with fewer normal sperm. Thus, high levels of PFAAs may contribute to the otherwise unexplained low semen quality often seen in young men. However, our findings need to be corroborated in larger studies.     

Association between urinary polycyclic aromatic hydrocarbon metabolites and sperm DNA damage: a population study in Chongqing, China

Background

Polycyclic aromatic hydrocarbons (PAHs), a class of the most ubiquitous environmental contaminants, may reduce male reproductive functions, but the data from human population studies are very limited.

Objectives

We designed this study to determine whether environmental exposure to PAHs contributes to the alteration in semen quality, sperm DNA damage, and apoptosis in the general male human population.

Methods

We measured urinary levels of four PAH metabolites and assessed semen quality, sperm apoptotic markers with Annexin V assay, and sperm DNA damage with comet assay in 232 men from Chongqing, China.

Results

We found that increased urinary 2-hydroxynaphthalene (2-OHNa) levels were associated with increased comet parameters, including the percentage of DNA in the tail (tail%) [β coefficient = 13.26% per log unit 2-OHNa (micrograms per gram creatinine); 95% confidence interval (CI), 7.97–18.55]; tail length (12.25; 95% CI, 0.01–24.52), and tail distribution (7.55; 95% CI, 1.28–18.83). The urinary level of 1-hydroxypyrene was associated only with increased tail% (5.32; 95% CI, 0.47–10.17). Additionally, the increased levels of four urinary PAH metabolites were significantly associated with decreased vital Annexin V negative sperm counts. However, there was no significant association between urinary PAH metabolite levels and human semen parameters or morphology of the sperm samples.

Conclusions

Our data indicate that the environmental level of PAH exposure is associated with increased sperm DNA damage but not with semen quality. These findings suggest that exposure to PAHs may disrupt sperm DNA and thereby interfere with human male fertility.     

Predictors of Serum Dioxins and PCBs among Peripubertal Russian Boys

Background

Although sources and routes of exposure to dioxins and polychlorinated biphenyls (PCBs) have been studied, information regarding exposure among children is limited. Breast-feeding and diet are two important contributors to early life exposure. To further understand other significant contributors to childhood exposure, we studied a cohort of children from a city with high environmental dioxin levels.

Objectives

We investigated predictors of serum concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs)/co-planar PCBs (C-PCBs), toxic equivalents (TEQs), and PCBs among 8- to 9-year-old boys in Chapaevsk, Russia.

Methods

We used general linear regression models to explore associations of log₁₀-transformed serum concentrations of PCDDs/PCDFs/C-PCBs, TEQs, and PCBs at study entry with anthropometric, demographic, geographic, and dietary factors in 482 boys in Chapaevsk, Russia.

Results

The median (25th, 75th percentile) concentration for total 2005 TEQs was 21.1 pg/g lipid (14.4, 33.2). Boys who were older, consumed local foods, were breast-fed longer, and whose mothers were employed at the Khimprom chemical plant (where chlorinated chemicals were produced) or gardened locally had significantly higher serum dioxins and PCBs, whereas boys with higher body mass index or more educated parents had significantly lower serum dioxins and PCBs. Boys who lived < 2 km from Khimprom had higher total TEQs (picograms per gram lipid) [adjusted mean = 30.6; 95% confidence interval (CI), 26.8–35.0] than boys who lived > 5 km away (adjusted mean = 18.8; 95% CI, 17.2–20.6).

Conclusions

Our findings suggest that there are specific local sources of dioxin and PCB exposure among children in Chapaevsk including maternal gardening, consumption of locally grown food, and residential proximity to the Khimprom plant.     

Urinary Concentrations of Parabens and Serum Hormone Levels,Semen Quality Parameters,and Sperm DNA Damage

Background

Parabens are commonly used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Widespread human exposure to parabens has been recently documented, and some parabens have demonstrated adverse effects on male reproduction in animal studies. However, human epidemiologic studies are lacking.

Objective

We investigated relationships between urinary concentrations of parabens and markers of male reproductive health in an ongoing reproductive epidemiology study.

Methods

Urine samples collected from male partners attending an infertility clinic were analyzed for methyl paraben (MP), propyl paraben (PP), butyl paraben (BP), and bisphenol A (BPA). Associations with serum hormone levels (n = 167), semen quality parameters (n = 190), and sperm DNA damage measures (n = 132) were assessed using multivariable linear regression.

Results

Detection rates in urine were 100% for MP, 92% for PP, and 32% for BP. We observed no statistically significant associations between MP or PP and the outcome measures. Categories of urinary BP concentration were not associated with hormone levels or conventional semen quality parameters, but they were positively associated with sperm DNA damage (p for trend = 0.03). When urinary BPA quartiles were added to the model, BP and BPA were both positively associated with sperm DNA damage (p for trend = 0.03). Assessment of paraben concentrations measured on repeated urine samples from a subset of the men (n = 78) revealed substantial temporal variability.

Conclusions

We found no evidence for a relationship between urinary parabens and hormone levels or semen quality, although intraindividual variability in exposure and a modest sample size could have limited our ability to detect subtle relationships. Our observation of a relationship between BP and sperm DNA damage warrants further investigation.     

Cadmium-Related Mortality and Long-Term Secular Trends in the Cadmium Body Burden of an Environmentally Exposed Population

Background

Few population studies have reported on the long-term changes in the internal cadmium dose and simultaneously occurring mortality.

Objective

We monitored blood cadmium (BCd), 24-hr urinary cadmium (UCd), and mortality in an environmentally exposed population.

Methods

Starting from 1985, we followed BCd (until 2003), UCd (until 1996), and mortality (until 2007) among 476 and 480 subjects, randomly recruited from low- exposure areas (LEA) and high-exposure areas (HEA). The last cadmium-producing plant in the HEA closed in 2002.

Results

From 1985–1989 to 1991–1996, BCd decreased by 40.3% and 18.9% in the LEA and HEA, respectively (p < 0.0001 for between-area difference). From 1991–1996 until 2001–2003, BCd remained unchanged in the HEA (+ 1.8%) and increased by 19.7% in the LEA (p < 0.0001). Over the entire follow-up period, the annual decrease in BCd averaged 2.7% in the LEA (n = 258) and 1.8% in the HEA (n = 203). From 1985–1989 to 1991–1996, UCd fell by 12.9% in the LEA and by 16.6% in the HEA (p = 0.22), with mean annual decreases of 2.7% (n = 366) and 3.4% (n = 364). Over 20.3 years (median), 206 deaths (21.5%) occurred. At baseline, BCd (14.6 vs. 10.2 nmol/L) and UCd (14.1 vs. 8.6 nmol/24-hr) were higher in deaths than in survivors. The risks (p ≤ 0.04) associated with a doubling of baseline UCd were 20% and 44% for total and noncardiovascular mortality, and 25% and 33% for a doubling of BCd.

Conclusions

Even if zinc–cadmium smelters close, historical environmental contamination remains a persistent source of exposure. Environmental exposure to cadmium increases total and noncardiovascular mortality in a continuous fashion without threshold.     

Serum Polybrominated Diphenyl Ether (PBDE) Levels Are Higher in Children (2–5 Years of Age) than in Infants and Adults

Background

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many products and have been detected in human samples worldwide. Limited data show that concentrations are elevated in young children.

Objectives

We investigated the association between PBDEs and age with an emphasis on young children from Australia in 2006–2007.

Methods

We collected human blood serum samples (n = 2,420), which we stratified by age and sex and pooled for analysis of PBDEs.

Results

The sum of BDE-47, -99, -100, and -153 concentrations (∑₄PBDE) increased from 0–0.5 years (mean ± SD, 14 ± 3.4 ng/g lipid) to peak at 2.6–3 years (51 ± 36 ng/g lipid; p < 0.001) and then decreased until 31–45 years (9.9 ± 1.6 ng/g lipid). We observed no further significant decrease among ages 31–45, 45–60 (p = 0.964), or > 60 years (p = 0.894). The mean ∑₄PBDE concentration in cord blood (24 ± 14 ng/g lipid) did not differ significantly from that in adult serum at ages 15–30 (p = 0.198) or 31–45 years (p = 0.140). We found no temporal trend when we compared the present results with Australian PBDE data from 2002–2005. PBDE concentrations were higher in males than in females; however, this difference reached statistical significance only for BDE-153 (p = 0.05).

Conclusions

The observed peak concentration at 2.6–3 years of age is later than the period when breast-feeding is typically ceased. This suggests that in addition to the exposure via human milk, young children have higher exposure to these chemicals and/or a lower capacity to eliminate them.     

Polycarbonate Bottle Use and Urinary Bisphenol A Concentrations

Background

Bisphenol A (BPA) is a high-production-volume chemical commonly used in the manufacture of polycarbonate plastic. Low-level concentrations of BPA in animals and possibly in humans may cause endocrine disruption. Whether ingestion of food or beverages from polycarbonate containers increases BPA concentrations in humans has not been studied.

Objectives

We examined the association between use of polycarbonate beverage containers and urinary BPA concentrations in humans.

Methods

We conducted a nonrandomized intervention of 77 Harvard College students to compare urinary BPA concentrations collected after a washout phase of 1 week to those taken after an intervention week during which most cold beverages were consumed from polycarbonate drinking bottles. Paired t-tests were used to assess the difference in urinary BPA concentrations before and after polycarbonate bottle use.

Results

The geometric mean urinary BPA concentration at the end of the washout phase was 1.2 μg/g creatinine, increasing to 2.0 μg/g creatinine after 1 week of polycarbonate bottle use. Urinary BPA concentrations increased by 69% after use of polycarbonate bottles (p < 0.0001). The association was stronger among participants who reported ≥ 90% compliance (77% increase; p < 0.0001) than among those reporting < 90% compliance (55% increase; p = 0.03), but this difference was not statistically significant (p = 0.54).

Conclusions

One week of polycarbonate bottle use increased urinary BPA concentrations by two-thirds. Regular consumption of cold beverages from polycarbonate bottles is associated with a substantial increase in urinary BPA concentrations irrespective of exposure to BPA from other sources.     

Lead Exposure and Behavior among Young Children in Chennai,India

Background

Lead exposure has long been associated with deficits in IQ among children. However, few studies have assessed the impact of lead on specific domains of behavior and cognition.

Objective

We evaluated the associations between lead and different domains of neurobehavior and their relative sensitivity to lead.

Methods

We determined blood lead levels using a LeadCare instrument in 756 children 3–7 years of age attending pre- and elementary schools in Chennai, India. Anxiety, social problems, inattention, hyperactivity, and attention deficit hyperactivity disorder (ADHD), as well as executive function were assessed in children by their schoolteachers using Conners’ Teacher Rating Scales-39, Conners’ ADHD/Diagnostic and Statistical Manual for Mental Disorders, 4th Edition Scales (CADS), and the Behavior Rating Inventory of Executive Function questionnaires, with higher scores denoting worse behavior. Analyses were carried out using multivariate generalized estimating equations with comparisons of outcome Z-scores to assess the relative strengths of the associations between log-blood lead and the different domains of behavior.

Results

Mean blood lead level was 11.4 ± 5.3 μg/dL. Blood lead was associated with higher anxiety (β = 0.27, p = 0.01), social problems (β = 0.20, p = 0.02), and higher scores in the ADHD index (β = 0.17; p = 0.05). The effect estimate was highest for global executive function (β = 0.42; p< 0.001).

Conclusions

Higher blood lead levels in this population of young children is associated with increased risk of neurobehavioral deficits and ADHD, with executive function and attention being particularly vulnerable domains to the effects of lead.     

Influence of Cobalamin on Arsenic Metabolism in Bangladesh

Background

Arsenic is a carcinogen to which 35 million people in Bangladesh are chronically exposed. The enzymatic transfer of methyl groups to inorganic As (iAs) generates monomethylarsonic (MMA) and dimethylarsinic acids (DMA) and facilitates urinary As (uAs) elimination. This process is dependent on one-carbon metabolism, a pathway in which folate and cobalamin have essential roles in the recruitment and transfer of methyl groups. Although DMA^V is the least toxic metabolite, increasing evidence suggests that MMA^III may be the most cytotoxic and genotoxic As intermediary metabolite.

Objective

We examined the associations between plasma cobalamin and uAs metabolites.

Methods

We conducted a cross-sectional study of 778 Bangladeshi adults in which we over-sampled cobalamin-deficient participants. Participants provided blood samples for the measurement of plasma cobalamin and urine specimens for As measurements.

Results

Cobalamin was inversely associated with the proportion of total uAs excreted as iAs (%iAs) [unstandardized regression coefficient (b) = –0.10; 95% confidence interval (CI), −0.17 to −0.02; p = 0.01] and positively associated with %MMA (b = 0.12; 95% CI, 0.05 to 0.20; p = 0.001). Both of these associations were stronger among folate-sufficient participants (%iAs: b = −0.17; 95% CI, −0.30 to −0.03; p = 0.02. %MMA: b = 0.20; 95% CI, 0.11 to 0.30; p < 0.0001), and the differences by folate status were statistically significant.

Conclusions

In this group of Bangladeshi adults, cobalamin appeared to facilitate the first As methylation step among folate-sufficient individuals. Given the toxicity of MMA^III, our findings suggest that in contrast to folate, cobalamin may not favorably influence As metabolism.     

Case-control study of blood lead levels and attention deficit hyperactivity disorder in Chinese children

Background

Attention deficit/hyperactivity disorder (ADHD) and lead exposure are high-prevalence conditions among children.

Objective

Our goal was to investigate the association between ADHD and blood lead levels (BLLs) in Chinese children, adjusting for known ADHD risk factors and potential confounding variables.

Methods

We conducted a pair-matching case–control study with 630 ADHD cases and 630 non-ADHD controls 4–12 years of age, matched on the same age, sex, and socioeconomic status. The case and control children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised criteria (DSM-IV-R). We evaluated the association between BLLs and ADHD using the Pearson chi-square test for categorical variables and the Student t-test for continuous data. We then performed conditional multiple variables logistic regression analyses with backward stepwise selection to predict risk factors for ADHD.

Results

There was a significant difference in BLLs between ADHD cases and controls. ADHD cases were more likely to have been exposed to lead during childhood than the non-ADHD control subjects, with adjustment for other known risk factors [children with BLLs ≥ 10 μg/dL vs. ≤ 5 μg/dL; OR = 6.0; 95% confidence interval (CI) = 4.10–8.77, p < 0.01; 5–10 μg/dL vs.≤ 5 μg/dL, OR = 4.9; 95% CI = 3.47–6.98, p < 0.01]. These results were not modified by age and sex variables.

Conclusions

This was the largest sample size case–control study to date to study the association between BLLs and ADHD in Chinese children. ADHD may be an additional deleterious outcome of lead exposure during childhood, even when BLLs are < 10 μg/dL.     

Daily Bisphenol A Excretion and Associations with Sex Hormone Concentrations: Results from the InCHIANTI Adult Population Study

Background

Bisphenol A (BPA) is a high production volume chemical widely used in packaging for food and beverages. Numerous studies have demonstrated that BPA can alter endocrine function in animals, yet human studies remain limited.

Objective

We estimated daily excretion of BPA among adults and examined hypothesized associations with serum estrogen and testosterone concentrations.

Methods

We conducted cross-sectional analyses using data from the InCHIANTI Study, a prospective population-based study of Italian adults. Our study included 715 adults between 20 and 74 years old. BPA concentrations were measured by liquid chromatography–mass spectrometry in 24-hr urine samples. The main outcome measures were serum concentrations of total testosterone and 17β-estradiol.

Results

Geometric mean urinary BPA concentration was 3.59 ng/mL [95% confidence interval (CI), 3.42–3.77 ng/mL], and mean excretion was 5.63 μg/day (5th population percentile, 2.1 μg/day; 95th percentile, 16.4 μg/day). We found higher excretion rates among men, younger respondents, and those with increasing waist circumference (p = 0.013) and weight (p = 0.003). Higher daily BPA excretion was associated with higher total testosterone concentrations in men, in models adjusted for age and study site (p = 0.044), and in models additionally adjusted for smoking, measures of obesity, and urinary creatinine concentrations (β = 0.046; 95% CI, 0.015–0.076; p = 0.004). We found no associations with the other serum measures. We also found no associations with the primary outcomes among women, but we did find an association between BPA and SHBG concentrations in the 60 premenopausal women.

Conclusion

Higher BPA exposure may be associated with endocrine changes in men. The mechanisms involved in the observed cross-sectional association with total testosterone concentrations need to be clarified.     

The Effect of Ambient Air Pollution on Sperm Quality

Background

Research has suggested an association with ambient air pollution and sperm quality.

Objectives

We investigated the effect of exposure to ozone (O₃) and particulate matter < 2.5 μm in aerodynamic diameter (PM_2.5) on sperm quality.

Methods

We reexamined a previous cohort study of water disinfection by-products to evaluate sperm quality in 228 presumed fertile men with different air pollution profiles. Outcomes included sperm concentration, total sperm per ejaculate (count), and morphology, as well as DNA integrity and chromatin maturity. Exposures to O₃ and PM_2.5 were evaluated for the 90–day period before sampling. We used multivariable linear regression, which included different levels of adjustment (i.e., without and with season and temperature) to assess the relationship between exposure to air pollutants during key periods of sperm development and adverse sperm outcomes.

Results

Sperm concentration and count were not associated with exposure to PM_2.5, but there was evidence of an association (but not statistically significant) with O₃ concentration and decreased sperm concentration and count. Additionally, a significant increase in the percentage of sperm cells with cytoplasmic drop [β = 2.64; 95% confidence interval (CI), 0.21–5.06] and abnormal head (β = 0.47; 95% CI, 0.03–0.92) was associated with PM_2.5 concentration in the base model. However, these associations, along with all other sperm outcomes, were not significantly associated with either pollutant after controlling for season and temperature. Overall, although we found both protective and adverse effects, there was generally no consistent pattern of increased abnormal sperm quality with elevated exposure to O₃ or PM_2.5.

Conclusions

Exposures to O₃ or PM_2.5 at levels below the current National Ambient Air Quality Standards were not associated with statistically significant decrements in sperm outcomes in this cohort of fertile men. However, some results suggested effects on sperm concentration, count, and morphology.     

Associations of Plasma Concentrations of Dichlorodiphenyldichloroethylene and Polychlorinated Biphenyls with Prostate Cancer: A Case–Control Study in Guadeloupe (French West Indies)

Background:

Long-term exposure to persistent pollutants with hormonal properties (endocrine-disrupting chemicals; EDCs) may contribute to the risk of prostate cancer (PCa). However, epidemiological evidence remains limited.

Objectives:

We investigated the relationship between PCa and plasma concentrations of universally widespread pollutants, in particular p,p´-dichlorodiphenyl dichloroethene (DDE) and the non-dioxin-like polychlorinated biphenyl congener 153 (PCB-153).

Methods:

We evaluated 576 men with newly diagnosed PCa (before treatment) and 655 controls in Guadeloupe (French West Indies). Exposure was analyzed according to case–control status. Associations were assessed by unconditional logistic regression analysis, controlling for confounding factors. Missing data were handled by multiple imputation.

Results:

We estimated a significant positive association between DDE and PCa [adjusted odds ratio (OR) = 1.53; 95% CI: 1.02, 2.30 for the highest vs. lowest quintile of exposure; p_trend = 0.01]. PCB-153 was inversely associated with PCa (OR = 0.30; 95% CI: 0.19, 0.47 for the highest vs. lowest quintile of exposure values; p_trend < 0.001). Also, PCB-153 was more strongly associated with low-grade than with high-grade PCa.

Conclusions:

Associations of PCa with DDE and PCB-153 were in opposite directions. This may reflect differences in the mechanisms of action of these EDCs; and although our findings need to be replicated in other populations, they are consistent with complex effects of EDCs on human health.

Citation:

Emeville E, Giusti A, Coumoul X, Thomé JP, Blanchet P, Multigner L. 2015. Associations of plasma concentrations of dichlorodiphenyldichloroethylene and polychlorinated biphenyls with prostate cancer: a case–control study in Guadeloupe (French West Indies). Environ Health Perspect 123:317–323; http://dx.doi.org/10.1289/ehp.1408407     

DDT Exposure of Zebrafish Embryos Enhances Seizure Susceptibility: Relationship to Fetal p,p′-DDE Burden and Domoic Acid Exposure of California Sea Lions

Background

California sea lions have a large body burden of organochlorine pesticides, and over the last decade they have also been subject to domoic acid poisoning. Domoic acid poisoning, previously recognized in adult animals, is now viewed as a major cause of prenatal mortality. The appearance of a chronic juvenile domoic acid disease in the sea lions, characterized by behavioral abnormalities and epilepsy, is consistent with early life poisoning and may be potentiated by organochlorine burden.

Objective

We investigated the interactive effect of DDT (dichlorodiphenyltrichloroethane) on neurodevelopment using a zebrafish (Danio rerio) model for seizure behavior to examine the susceptibility to domoic acid–induced seizures after completion of neurodevelopment.

Methods

Embryos were exposed (6–30 hr postfertilization) to either o,p′-DDT or p,p′-DDE (dichlorodiphenyldichloroethylene) during neurodevelopment via a 0.1% dimethyl sulfoxide solution. These larval (7 days postfertilization) fish were then exposed to either the seizure-inducing drug pentylenetetrazol (PTZ) or domoic acid; resulting seizure behavior was monitored and analyzed for changes using cameras and behavioral tracking software.

Results

Embryonic exposure to DDTs enhanced PTZ seizures and caused distinct and increased seizure behaviors to domoic acid, most notably a type of head-shaking behavior.

Conclusion

These studies demonstrate that embryonic exposure to DDTs leads to asymptomatic animals at completion of neurodevelopment with greater sensitivity to domoic acid–induced seizures. The body burden levels of p,p′-DDE are close to the range recently found in fetal California sea lions and suggest a potential interactive effect of p,p′-DDE embryonic poisoning and domoic acid toxicity.     

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.     

Maternal Exposure to a Brominated Flame Retardant and Genitourinary Conditions in Male Offspring

Background

The upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor.

Objective

We investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero.

Methods

In this cohort study of sons born to women accidentally exposed to PBBs during 1973–1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth.

Results

Of 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [≤1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8–5.1]. This risk was increased when we excluded sons born after the exposure but before the mother’s serum PBB measurement (OR = 3.1; 95% CI, 1.0–9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure.

Conclusions

Although cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.     

The relationship between prenatal PCB exposure and intelligence (IQ) in 9-year-old children

Background

Several epidemiologic studies have demonstrated relationships between prenatal exposure to polychlorinated biphenyls (PCBs) and modest cognitive impairments in infancy and early childhood. However, few studies have followed cohorts of exposed children long enough to examine the possible impact of prenatal PCB exposure on psychometric intelligence in later childhood. Of the few studies that have done so, one in the Great Lakes region of the United States reported impaired IQ in children prenatally exposed to PCBs, whereas another found no association.

Objectives

This study was designed to determine whether environmental exposure to PCBs predicts lower IQ in school-age children in the Great Lakes region of the northeastern United States.

Methods

We measured prenatal exposure to PCBs and IQ at 9 years of age in 156 subjects from Oswego, New York. We also measured > 50 potential predictors of intelligence in children, including repeated measures of the home environment [Home Observation for Measurement of the Environment (HOME)], socioeconomic status (SES), parental IQ, alcohol/cigarette use, neonatal risk factors, and nutrition.

Results

For each 1-ng/g (wet weight) increase in PCBs in placental tissue, Full Scale IQ dropped by three points (p = 0.02), and Verbal IQ dropped by four points (p = 0.003). The median PCB level was 1.50 ng/g, with a lower quartile of 1.00 ng/g and an upper quartile of 2.06 ng/g. Moreover, this association was significant after controlling for many potential confounders, including prenatal exposure to methylmercury, dichlorodiphenyldichloroethylene, hexachlorobenzene, and lead.

Conclusions

These results, in combination with similar results obtained from a similar study in the Great Lakes conducted 10 years earlier, indicate that prenatal PCB exposure in the Great Lakes region is associated with lower IQ in children.     

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.     

Selecting Adequate Exposure Biomarkers of Diisononyl and Diisodecyl Phthalates: Data from the 2005–2006 National Health and Nutrition Examination Survey

Background

High-molecular-weight phthalates, such as diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers.

Objectives

We assessed exposure to DINP and DIDP in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005–2006 National Health and Nutrition Examination Survey (NHANES).

Methods

We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography–tandem mass spectrometry.

Results

We detected monocarboxyisooctyl phthalate (MCOP), a metabolite of DINP, and monocarboxyisononyl phthalate (MCNP), a metabolite of DIDP, in 95.2% and 89.9% of the samples, respectively. We detected monoisononyl phthalate (MNP), a minor metabolite of DINP, much less frequently (12.9%) and at concentration ranges (> 0.8 μg/L–148.1 μg/L) much lower than MCOP (> 0.7 μg/L– 4,961 μg/L). Adjusted geometric mean concentrations of MCOP and MCNP were significantly higher (p < 0.01) among children than among adolescents and adults.

Conclusions

The general U.S. population, including children, was exposed to DINP and DIDP. In previous NHANES cycles, the occurrence of human exposure to DINP by using MNP as the sole urinary biomarker has been underestimated, thus illustrating the importance of selecting the most adequate biomarkers for exposure assessment.     

The influence of living near roadways on spirometry and exhaled nitric oxide in elementary schoolchildren

Background

Living near major roadways has been associated with an increase in respiratory symptoms, but little is known about how this relates to airway inflammation.

Objective

We assessed the effects of living near local residential roadways based on objective indicators of ventilatory function and airway inflammation.

Methods

We estimated ambient air pollution, resolved to the level of the child’s neighborhood, using a land-use regression model for children 9–11 years of age. We also summed the length of roadways found within a 200-m radius of each child’s neighborhood. We had measurements of both air pollution exposure and spirometry for 2,328 children, and also had measurements of exhaled nitric oxide (eNO) for 1,613 of these children.

Results

Each kilometer of local roadway within a 200-m radius of the home was associated with a 6.8% increase in eNO (p = 0.045). Each kilometer of any type of roadway (local, major, highway) was also associated with an increase in eNO of 10.1% (p = 0.002). Each microgram per cubic meter increase in PM_2.5 was associated with a 3.9% increase in eNO (p = 0.058) and 0.70% decrease in forced vital capacity (FVC) expressed as a percentage of predicted (p = 0.39). Associations between roadway density and both forced expired volume in 1 sec and FVC were negative but not statistically significant at p < 0.05.

Conclusion

Traffic from local neighborhood roadways may cause airway inflammation as indicated by eNO. This may be a more sensitive indicator of adverse air pollution effects than traditional measures of ventilatory function.