Search

Background: Recent data indicate that chronic low-level exposure to lead is associated with accelerated declines in cognition in older age, but this has not been examined in women., Objective: We examined biomarkers of lead exposure in relation to performance on a battery of cognitive tests among older women., Methods: Patella and tibia bone lead--measures of cumulative exposure over many years--and blood lead, a measure of recent exposure, were assessed in 587 women 47-74 years of age. We assessed their cognitive function 5 years later using validated telephone interviews., Results: Mean +/- SD lead levels in tibia, patella, and blood were 10.5 +/- 9.7 microg/g bone, 12.6 +/- 11.6 microg/g bone, and 2.9 +/- 1.9 microg/dL, respectively, consistent with community-level exposures. In multivariable-adjusted analyses of all cognitive tests combined, levels of all three lead biomarkers were associated with worse cognitive performance. The association between bone lead and letter fluency score differed dramatically from the other bone lead-cognitive score associations, and exclusion of this particular score from the combined analyses strengthened the associations between bone lead and cognitive performance. Results were statistically significant only for tibia lead: one SD increase in tibia lead corresponded to a 0.051-unit lower standardized summary cognitive score (95% confidence interval: -0.099 to -0.003; p = 0.04), similar to the difference in cognitive scores we observed between women who were 3 years apart in age., Conclusions: These findings suggest that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women's cognition in older age.

Background: Urinary arsenic metabolites (UAs) are used as biomarkers of exposure and metabolism., Objectives: To characterize inter- and intraindividual variability in UAs in healthy individuals., Methods: In a longitudinal study conducted in Bangladesh, we collected water and spot urine samples from 196 participants every 3 months for 2 years. Water arsenic (As) was measured by inductively coupled plasma-mass spectrometry and urinary As [arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were detected using high-performance liquid chromatography-hydride-generated atomic absorption spectrometry. We used linear mixed-effects models to compute variance components and evaluate the association between UAs and selected factors., Results: The concentrations of UAs were fairly reproducible within individuals, with intraclass correlation coefficients (ICCs) of 0.41, 0.35, 0.47, and 0.49 for inorganic As (InAs), MMA, DMA, and total urinary As (TUA). However, when expressed as a ratio, the percent InAs (%InAs), %MMA, and %DMA were poorly reproducible within individuals, with ICCs of 0.16, 0.16, and 0.17, respectively. Arsenic metabolism was significantly associated with sex, exposure, age, smoking, chewing betel nut, urinary creatinine, and season. Specificity and sensitivity analyses showed that a single urine sample adequately classified a participant's urinary As profile as high or low, but TUA had only moderate specificity for correctly classifying drinking water exposures., Conclusions: Epidemiologic studies should use both urinary As concentrations and the relative proportion of UAs to minimize measurement error and to facilitate interpretation of factors that influence As metabolism.

The classical statistical paradigm emphasizes the development and application of methods to account for sampling variability. Many modern day applications, however, require consideration of other sources of uncertainty that are not so easy to quantify. This paper presents a case study involving an assessment of the impact of in-utero methylmercury exposure on the Intelligence Quotient (IQ) of young children. We illustrate how familiar techniques such as hierarchical modeling, Bayesian methods and sensitivity analysis can be used to aid decision making in settings that involve substantial uncertainty.

Objective: Chronic psychosocial stressors, including violence, and neuropsychological and behavioral development in children as well as physiologic alterations that may lead to broader health effects., Methods: We studied the relationship between violence and childhood lung function in a prospective birth cohort of 313 urban children (age range = 6-7 years). Mothers reported on their child's lifetime exposure to community violence (ETV) and interparental conflict in the home (Conflict Tactics Scale (CTS)) within 1 year of the lung function assessment., Results: In linear regression analyses, adjusting for maternal education, child's age, race, birthweight, tobacco smoke exposure, and medical history, girls in the highest CTS verbal aggression tertile had a 5.5% (95% confidence interval (CI) = -9.6, -1.5) decrease in percent predicted forced expiratory volume (FEV(1)) and a 5.4% (95% CI = -9.7, -1.1) decrease in forced vital capacity (FVC) compared with girls in the lowest tertile. The CTS verbal aggression subscale was associated with lung function among boys in the same direction, albeit this was not statistically significant. Boys in the highest ETV tertile had a 3.4% (95% CI = -8.0, 1.1) lower FEV(1) and 5.3% lower FVC (95% CI = -10.2, -0.4) compared with boys in the lowest tertile. The ETV score was not a significant predictor of girls' lung function., Conclusions: Interparental conflict, specifically verbal aggression, and ETV were associated with decreased childhood lung function independent of socioeconomic status, tobacco smoke exposure, birthweight, and respiratory illness history. Gender differences were noted based on the type of violence exposure, which may warrant further exploration.

Background: There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age., Objectives: To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children., Methods: Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area., Results: In multivariate analyses, early exposure to high levels of dust mite allergen (> or =10 microg/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% CI, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages 1 and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43)., Conclusion: Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze., Clinical Implications: Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children.

We assessed determinants of cord serum polychlorinated biphenyl (PCB) levels among 720 infants born between 1993 and 1998 to mothers living near a PCB-contaminated Superfund site in Massachusetts, measuring the sum of 51 PCB congeners (capital sigmaPCB) and ascertaining maternal address, diet, sociodemographics, and exposure risk factors. Addresses were geocoded to obtain distance to the Superfund site and neighborhood characteristics. We modeled log10(capital sigmaPCB) as a function of potential individual and neighborhood risk factors, mapping model residuals to assess spatial correlates of PCB exposure. Similar analyses were performed for light (mono-tetra) and heavy (penta-deca) PCBs to assess potential differences in exposure pathways as a function of relative volatility. PCB-118 (relatively prevalent in site sediments and cord serum) was assessed separately. The geometric mean of capital sigmaPCB levels was 0.40 (range, 0.068-18.14) ng/g serum. Maternal age and birthplace were the strongest predictors of capital sigmaPCB levels. Maternal consumption of organ meat and local dairy products was associated with higher and smoking and previous lactation with lower capital sigmaPCB levels. Infants born later in the study had lower capital sigmaPCB levels, likely due to temporal declines in exposure and site remediation in 1994-1995. No association was found between capital sigmaPCB levels and residential distance from the Superfund site. Similar results were found with light and heavy PCBs and PCB-118. Previously reported demographic (age) and other (lactation, smoking, diet) correlates of PCB exposure, as well as local factors (consumption of local dairy products and Superfund site dredging) but not residential proximity to the site, were important determinants of cord serum PCB levels in the study community.

Widespread application of contemporary-use insecticides results in low-level exposure for a majority of the population through a variety of pathways. Urinary insecticide biomarkers account for all exposure pathways, but failure to account for temporal within-subject variability of urinary levels can lead to exposure misclassification. To examine temporal variability in urinary markers of contemporary-use insecticides, nine repeated urine samples were collected over 3 months from 10 men participating in an ongoing study of male reproductive health. These 90 samples were analyzed for urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPY)) and carbaryl (1-naphthol (1N)). Volume- based (unadjusted), as well as creatinine (CRE)- and specific gravity (SG)-adjusted concentrations were measured. TCPY had low reliability with an intraclass correlation coefficient between 0.15 and 0.21, while 1N was moderately reliable with an intraclass correlation coefficient between 0.55 and 0.61. When the 10 men were divided into tertiles based on 3-month geometric mean TCPY and 1N levels, a single urine sample performed adequately in classifying a subject into the highest or lowest exposure tertiles. Sensitivity and specificity ranged from 0.44 to 0.84 for TCPY and from 0.56 to 0.89 for 1N. Some differences in the results between unadjusted metabolite concentrations and concentrations adjusted for CRE and SG were observed. Questionnaires were used to assess diet in the 24 h preceding the collection of each urine sample. In mixed-effects models, TCPY was significantly associated with season as well as with consuming grapes and cheese, while 1N levels were associated with consuming strawberries. In conclusion, although a single sample adequately predicted longer-term average exposure, a second sample collected at least 1 month following the first sample would reduce exposure measurement error.

Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a +/-10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (beta = -0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (beta = -0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.

Background: Phthalates are used in personal and consumer products, food packaging materials, and polyvinyl chloride plastics and have been measured in the majority of the general population of the USA. Consistent experimental evidence shows that some phthalates are developmental and reproductive toxicants in animals. This study explored the association between environmental levels of phthalates and altered reproductive hormone levels in adult men., Methods: Between 1999 and 2003, 295 men were recruited from Massachusetts General Hospital. Selected phthalate metabolites were measured in urine. Linear regression models explored the relationship between specific gravity-adjusted urinary phthalate monoester concentrations and serum levels of reproductive hormones, including FSH, LH, sex hormone-binding globulin, testosterone, and inhibin B., Results: An interquartile range (IQR) change in monobenzyl phthalate (MBzP) exposure was significantly associated with a 10% [95% confidence interval (CI): -16, -4.0] decrease in FSH concentration. Additionally, an IQR change in monobutyl phthalate (MBP) exposure was associated with a 4.8% (95% CI: 0, 10) increase in inhibin B but this was of borderline significance., Conclusions: Although we found associations between MBP and MBzP urinary concentrations and altered levels of inhibin B and FSH, the hormone concentrations did not change in the expected patterns. Therefore, it is unclear whether these associations represent physiologically relevant alterations in these hormones, or whether they represent associations found as a result of conducting multiple comparisons.

Most of the general population is exposed to carbaryl and other contemporary-use insecticides at low levels. Studies of laboratory animals, in addition to limited human data, show an association between carbaryl exposure and decreased semen quality. In the present study we explored whether environmental exposures to 1-naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are associated with decreased semen quality in humans. Subjects (n=272) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary concentrations of 1N and TCPY adjusted using specific gravity. Semen quality was assessed as sperm concentration, percent motile sperm, and percent sperm with normal morphology, along with sperm motion parameters (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N concentrations were 3.22 and 3.19microg/L, respectively. For increasing 1N tertiles, adjusted odds ratios (ORs) were significantly elevated for below-reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2, 4.2, respectively; p-value for trend =0.01) and percent motile sperm (1.0, 2.5, 2.4; p-value for trend = 0.01). The sperm motion parameter most strongly associated with 1N was straight-line velocity. There were suggestive, borderline-significant associations for TCPY with sperm concentration and motility, whereas sperm morphology was weakly and nonsignificantly associated with both TCPY and 1N. The observed associations between altered semen quality and 1N are consistent with previous studies of carbaryl exposure, although suggestive associations with TCPY are difficult to interpret because human and animal data are currently limited.

Results of studies on paternal smoking and spontaneous abortions have been inconsistent. The authors examined the effect of paternal smoking on the risk of pregnancy loss in a prospective cohort of 526 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy. Daily urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy losses, and pregnancies were followed to detect clinical spontaneous abortions. Subjects were grouped by the number of cigarettes that husbands reported smoking daily: nonsmokers (group 1, n = 216), fewer than 20 cigarettes (group 2, n = 239), and 20 or more cigarettes (group 3, n = 71). Compared with that for group 1, the adjusted odds ratio of early pregnancy loss of any conception for group 2 was 1.04 (95% confidence interval (CI): 0.67, 1.63) and for group 3 was 1.81 (95% CI: 1.00, 3.29). The adjusted hazard ratio of conception for group 2 was 0.90 (95% CI: 0.70, 1.18) and for group 3 was 0.96 (95% CI: 0.66, 1.39), while the adjusted hazard ratio of clinical pregnancy for group 2 was 0.93 (95% CI: 0.72, 1.20) and for group 3 was 0.78 (95% CI: 0.55, 1.12). The authors conclude that heavy paternal smoking increased the risk of early pregnancy loss through maternal and/or paternal exposure.

The general population is exposed to phthalates through consumer products, diet, and medical devices. The present study explored whether phthalates, reproductive toxins in laboratory animals, were associated with altered sperm movement characteristics in men. Two-hundred twenty subjects provided a semen sample for computer-aided sperm analysis (CASA) and a urine sample for measurement of phthalate monoesters, monoethyl (MEP), monobenzyl (MBzP), mono-n-butyl (MBP), mono-2-ethylhexyl (MEHP), and monomethyl (MMP). Three CASA parameters, straight-line velocity (VSL), curvilinear velocity (VCL), and linearity (LIN), were used as measures of sperm progression, sperm vigor, and swimming pattern, respectively. There were suggestive dose-response relationships (shown as the predicted change in mean sperm motion parameter for the second and third tertiles compared with the first tertile; P value for trend) for MBzP with VSL (-2.36 microm/s, -2.81 microm/s; P =.09) and VCL (-1.67 microm/s, -2.45 microm/s; P =.4). There were suggestive negative associations between MBP and VSL (-3.07 microm/s, -2.87 microm/s; P =.08) and VCL (-3.25 microm/s, -3.46 microm/s; P =.2), and between MEHP with VSL (-1.09 microm/s, -2.73 microm/s; P =.1) and VCL (-0.29 microm/s, -2.93 microm/s; P =.3). In contrast to the other phthalates, MEP was positively associated with VSL and VCL but negatively associated with LIN. No consistent relationship was found for MMP and any sperm motion parameter. Although we did not find statistically significant associations, trends between CASA parameters, sperm velocity, and forward progression, and increased urinary levels of MBP, MBzP, and MEHP warrant further follow-up.

Air pollution standards and control strategies are based on ambient measurements. For many outdoor air pollutants, individuals are closer to their sources (especially traffic) and there are important indoor sources influencing the relationship between ambient and personal exposures. This paper examines the relationship between volatile organic compounds (VOCs) measured at central site monitoring stations and personal exposures in the Mexico City Metropolitan Area. Over a 1-year period, personal exposures to 34 VOCs were measured for 90 volunteers from 30 families living close to one of five central monitoring stations. Simultaneous 24-h indoor, outdoor and central site measurements were also taken. Dual packed thermal desorption tubes and C(18) DNPH-coated cartridges were used for sampling VOCs and these were analyzed by GC/MS and HPLC, respectively. A factor analysis of the personal exposure data aided in grouping compounds by the most likely source type: vehicular (BTEX, styrene and 1,3-butadiene), secondary formed or photochemical (most aldehydes), building materials and consumer products (formaldehyde and benzaldehyde), cleaning solvents (tetrachloroethene and 1,1,1-trichloroethane), volatilization from water (chloroform and trichloroethene) and deodorizers (1,4-dichlorobenzene). Mean ambient, indoor and personal concentrations were 7/7/14 microg/m(3) for benzene, 1/3/3 for 1,3-butadiene, 6/20/20 for formaldehyde and 3/9/50 for 1,4-dichlorobenzene. Geometric mean (GM) ambient concentrations of trichloroethene and carbon tetrachloride were similar to GM personal exposures. While outdoor and indoor home GM concentrations for most vehicular related compounds (benzene, MTBE, xylenes and styrene) were comparable, the GM personal exposures were twice as high. Indoor concentrations of 1,3-butadiene, 1,1,1-trichloroethane, tetrachloroethane, chloroform, formaldehyde, valeraldehyde, propionaldehyde and n-butyraldehyde were comparable to personal exposures. For certain compounds, such as chloroform, aldehydes, toluene, 1,3-butadiene and 1,4-dichlorobenzene, GM personal exposures were more than two times greater than GM ambient measurements.

Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and p,p -DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and p-value for trend were, respectively, 1.00, 1.68, 2.35, and p-value = 0.03) and morphology (1.00, 1.36, 2.53, p-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between p,p -DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners.

Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm.

Background: There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are associated with altered semen quality in humans., Methods: We recruited 168 men who were part of subfertile couples and who presented to the Massachusetts General Hospital andrology laboratory for semen analysis between January 2000 and April 2001. Semen parameters were dichotomized based on 1999 World Health Organization reference values for sperm concentration (< 20 million/ml) and motility (< 50% motile), as well as Tygerberg Strict criteria for morphology (< 4% normal). The comparison group was men for whom these semen parameters were all above the reference values. In urine, eight phthalate metabolites were measured with high-performance liquid chromatography and tandem mass spectrometry. Specific gravity-adjusted phthalate metabolite levels were categorized into tertiles., Results: There was a dose-response relation between tertiles of mono-butyl phthalate and sperm motility (odds ratio per tertile = 1.0, 1.8, 3.0; P-value for trend = 0.02) and sperm concentration (1.0, 1.4, 3.3; P-value for trend = 0.07). In addition, there was a dose-response relation between tertiles of mono-benzyl phthalate and sperm concentration (1.0, 1.4, 5.5; P-value for trend = 0.02)., Conclusions: There were dose-response relations for monobutyl phthalate and monobenzyl phthalate with one or more semen parameters, and suggestive evidence for monomethyl phthalate with sperm morphology. The lack of a relation for other phthalates may indicate a difference in spermatotoxicity among phthalates.

Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma.

Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.

There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress.

Background: Evaluation of expert assessment of exposure depends, in the absence of a validation measurement, upon measures of agreement among the expert raters. Agreement is typically measured using Cohen's Kappa statistic, however, there are some well-known limitations to this approach. We demonstrate an alternate method that uses log-linear models designed to model agreement. These models contain parameters that distinguish between exact agreement (diagonals of agreement matrix) and non-exact associations (off-diagonals). In addition, they can incorporate covariates to examine whether agreement differs across strata. Methods: We applied these models to evaluate agreement among expert ratings of exposure to sensitizers (none, likely, high) in a study of occupational asthma. Results: Traditional analyses using weighted kappa suggested potential differences in agreement by blue/white collar jobs and office/non-office jobs, but not case/control status. However, the evaluation of the covariates and their interaction terms in log-linear models found no differences in agreement with these covariates and provided evidence that the differences observed using kappa were the result of marginal differences in the distribution of ratings rather than differences in agreement. Differences in agreement were predicted across the exposure scale, with the likely moderately exposed category more difficult for the experts to differentiate from the highly exposed category than from the unexposed category. Conclusions: The log-linear models provided valuable information about patterns of agreement and the structure of the data that were not revealed in analyses using kappa. The models' lack of dependence on marginal distributions and the ease of evaluating covariates allow reliable detection of observational bias in exposure data. [ABSTRACT FROM AUTHOR]

Background: Previous studies linking violence exposure to adverse child behavior have typically relied on parental report of child symptoms without accounting for the informant's mental well-being, despite evidence that parental mental health can influence children's mental health and the parent's report of distress symptoms. Purpose: We assess the influence of maternal depression on the violence exposure and child distress association in a subset of the Maternal Infant Smoking Study of East Boston, a prospective birth cohort. Methods: Mothers reported on their children's violence exposure using the Survey of Children's Exposure to Community Violence (ETV) and completed the Checklist of Child Distress Symptoms (CCDS). The children also completed the ETV survey and the self-report version of the CCDS. Linear regression was used to assess the influence of violence exposure on distress symptoms adjusting for potential confounders, first using parent's report of exposure and outcome and a second time using the child's self-report. The mediating effect of maternal depression on the violence and distress association was also tested. Results: Among the 162 children ages 7 to 11, 51% were boys and 43% self-identified as Hispanic. When using child self-report, increased violence exposure was significantly associated with a broader range of distress symptoms (numbness, arousal, intrusion, avoidance subscales) compared to parent reported findings, which were only significantly related to the intrusion and avoidance subscales. Moreover, a significant mediation effect of maternal depression on the violence and distress association was noted only when mother's report of exposure and outcome was used. Conclusion: Considering both parent and child self-report of violence is necessary to obtain a complete picture of violence exposure because parents and children may be offering different, although equally valid information. The influence of maternal depressive symptoms on preadolescent's distress symptoms may be attributed to reporting bias as opposed to more direct effects; thus, the parent's psychological functioning should be taken into consideration when relying on parental report of the child's psychological functioning. [ABSTRACT FROM AUTHOR]

An important component of quantitative risk assessment involves characterizing the dose-response relationship between an environmental exposure and adverse health outcome and then computing a benchmark dose, or the exposure level that yields a suitably low risk. This task is often complicated by model choice considerations, because risk estimates depend on the model parameters. We propose using Bayesian methods to address the problem of model selection and derive a model-averaged version of the benchmark dose. We illustrate the methods through application to data on arsenic-induced lung cancer from Taiwan. [ABSTRACT FROM AUTHOR]

Low maternal prepregnancy BMI is associated with adverse birth outcomes, but the BMI at which risk increases is not well defined. We assessed whether the relationship between prepregnancy BMI and birth outcomes is influenced by the extent to which mothers were underweight in a prospective study in Anhui, China. The women (n = 575) were 20-34 y old, married, nulliparous and nonsmokers. All measures of infant growth increased with increasing maternal BMI until a plateau was reached at a BMI of 22-23 kg/m2. Infants born to the 27% of women who were severely underweight before pregnancy (BMI < or = 18.5 kg/m2) were at increased risk for fetal growth deficits associated with infant morbidity. Compared with a normal BMI, being severely underweight was associated with mean (+/- SEM) reductions of 219 +/- 40 g in infant birthweight and 6.7 +/- 1.3% in the birthweight ratio and an 80% increase in risk of intrauterine growth restriction [odds ratio (OR) 1.8; 95% CI: 1.0, 3.3; P = 0.05]. Being severely underweight was also associated with smaller infant head circumference and lower ponderal index. Being moderately underweight (18.5 < BMI < 19.8 kg/m2) was not significantly associated with adverse pregnancy outcomes. Gestational age and risk of preterm birth were not associated with maternal BMI. More than half of the women in this study were underweight before pregnancy. Although being moderately underweight was not associated with increased risk of adverse pregnancy outcomes, being severely underweight was an important risk factor for reduced fetal growth. [ABSTRACT FROM AUTHOR]

This study investigated whether the association between low level benzene exposure and shortened gestation is modified by two susceptibility genes, CYP1A1 and GSTT1. This report includes 542 (302 nonexposed, 240 benzene-exposed) nonsmoking and nondrinking mothers of singleton live births at Beijing Yanshan Petrochemical Corporation between June 1995 and June 1997. Epidemiologic and clinical data and blood samples were obtained from mothers. Multiple linear regression models were used to estimate the associations of benzene exposure and genetic susceptibility with gestational age, adjusting for maternal age, education, parity, stress, passive smoking, prepregnancy weight and height, and infant's sex. Without consideration of genotype, benzene exposure was associated with a decrease in mean gestational age of 0.29 (standard error (SE), 0.12) week. When stratified by the maternal CYP1A1 genotype, the estimated decrease was 0.54 (SE, 0.12) week for the AA group, which was significantly greater (p = 0.003) than that for the Aa/aa group, which showed no decrease in gestational age. When both CYP1A1 and GSTT1 were considered, the greatest decrease was found among exposed mothers with the CYP1A1 AA-GSTT1 absent group (0.79 (SE, 0.25) week) and the CYP1A1 AA-GSTT1 present group (0.50 (SE, 0.22) week). Among the nonexposed, genetic susceptibility alone did not confer a significant adverse effect. This study provides evidence of gene-environment interaction and supports further assessment of the role of genetic susceptibility in the evaluation of reproductive toxins. Am J Epidemiol 2000;152:693–700. [ABSTRACT FROM PUBLISHER]