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2.  Concentrations of Phthalate Metabolites in Milk, Urine, Saliva, and Serum of Lactating North Carolina Women 
Background
Phthalates are ubiquitous in the environment, but concentrations in multiple media from breast-feeding U.S. women have not been evaluated.
Objectives
The objective of this study was to accurately measure and compare the concentrations of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women.
Methods
We analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters.
Results
We detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3–22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concentration in urine. Metabolite concentrations differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride levels were increased among women with higher concentrations of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concentrations.
Conclusions
Our data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concentrations reflect maternal exposure and do not represent the concentrations of oxidative metabolites in other body fluids, especially milk.
doi:10.1289/ehp.11610
PMCID: PMC2627871  PMID: 19165392
biomonitoring; breast milk; lactation; MAMA study; phthalates; saliva; serum; urine
3.  Meeting Report: Measuring Endocrine-Sensitive Endpoints within the First Years of Life 
Environmental Health Perspectives  2008;116(7):948-951.
An international workshop titled “Assessing Endocrine-Related Endpoints within the First Years of Life” was held 30 April–1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove to develop or recommend standardized measurements that would allow comparisons and pooling of data across studies. The recommended outcomes include thigh fat fold, breast size, vaginal cytology, AGD, location of the testis, testicular size, and growth of the penis, with most of the discussion focusing on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions.
doi:10.1289/ehp.11226
PMCID: PMC2453165  PMID: 18629319
anogenital distance; anthropometry; endocrine disruptors; genital exam; hormones; infants; measurement; neurodevelopment; reproductive tract development; sexual dimorphism
4.  A Time Series Analysis of Air Pollution and Preterm Birth in Pennsylvania, 1997–2001 
Environmental Health Perspectives  2005;113(5):602-606.
Preterm delivery can lead to serious infant health outcomes, including death and lifelong disability. Small increases in preterm delivery risk in relation to spatial gradients of air pollution have been reported, but previous studies may have controlled inadequately for individual factors. Using a time-series analysis, which eliminates potential confounding by individual risk factors that do not change over short periods of time, we investigated the effect of ambient outdoor particulate matter with diameter ≤10 μm (PM10) and sulfur dioxide on risk for preterm delivery. Daily counts of preterm births were obtained from birth records in four Pennsylvania counties from 1997 through 2001. We observed increased risk for preterm delivery with exposure to average PM10 and SO2 in the 6 weeks before birth [respectively, relative risk (RR) = 1.07; 95% confidence interval (CI), 0.98–1.18 per 50 μg/m3 increase; RR = 1.15; 95% CI, 1.00–1. 32 per 15 ppb increase], adjusting for long-term preterm delivery trends, co-pollutants, and offsetting by the number of gestations at risk. We also examined lags up to 7 days before the birth and found an acute effect of exposure to PM10 2 days and 5 days before birth (respectively, RR = 1.10; 95% CI, 1.00–1.21; RR = 1.07; 95% CI, 0.98–1.18) and SO2 3 days before birth (RR = 1.07; 95% CI, 0.99–1.15), adjusting for covariates, including temperature, dew point temperature, and day of the week. The results from this time-series analysis, which provides evidence of an increase in preterm birth risk with exposure to PM10 and SO2, are consistent with prior investigations of spatial contrasts.
doi:10.1289/ehp.7646
PMCID: PMC1257554  PMID: 15866770
air pollution; environmental epidemiology; particulate matter; pregnancy; preterm birth; sulfur dioxide
5.  Use of biomarkers to indicate exposure of children to organophosphate pesticides: implications for a longitudinal study of children's environmental health. 
Environmental Health Perspectives  2003;111(16):1939-1946.
Because of their history of widespread use in the United States and unknown long-term health effects, organophosphate pesticides (OPs) are being considered as a chemical class of interest in planning for the National Children's Study, a longitudinal study of children's environmental health. The availability and appropriate use of biomarkers to determine absorbed doses of environmental chemicals such as OPs are critical issues. Biomarkers of OP exposure are typically measured in blood and urine; however, postpartum meconium has been shown to be a promising matrix for assessing cumulative in utero exposure to the fetus, and studies are currently in progress to determine the utility of using saliva and amniotic fluid as matrices. In this article, we discuss the advantages and disadvantages of the currently available OP exposure monitoring methods (cholinesterase inhibition in blood, pesticides in blood, metabolites in urine and alternative matrices); study design issues for a large, long-term study of children's environmental health; and current research and future research needs. Because OPs are rapidly metabolized and excreted, the utility of one-time spot measurements of OP biomarkers is questionable unless background exposure levels are relatively stable over time or a specific time frame of interest for the study is identified and samples are collected accordingly. Biomarkers of OP exposure can be a valuable tool in epidemiology of children's environmental health, as long as they are applied and interpreted appropriately.
PMCID: PMC1241770  PMID: 14644670
6.  Chlorination by-products in drinking water and menstrual cycle function. 
Environmental Health Perspectives  2003;111(7):935-941.
We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to explore further the effects of trihalomethanes (THM) on reproductive end points. Premenopausal women ((italic)n(/italic) = 403) collected urine samples daily during an average of 5.6 cycles for measurement of steroid metabolites that were used to define menstrual parameters such as cycle and phase length. Women were asked about consumption of various types of water as well as other habits and demographics. A THM level was estimated for each cycle based on residence and quarterly measurements made by water utilities during a 90-day period beginning 60 days before the cycle start date. We found a monotonic decrease in mean cycle length with increasing total THM (TTHM) level; at > 60 microg/L, the adjusted decrement was 1.1 days [95% confidence interval (CI), -1.8 to -0.40], compared with less than or equal to 40 microg/L. This finding was also reflected as a reduced follicular phase length (difference -0.94 day; 95% CI, -1.6 to -0.24). A decrement in cycle and follicular phase length of 0.18 days (95% CI, -0.29 to -0.07) per 10 microg/L unit increase in TTHM concentration was found. There was little association with luteal phase length, menses length, or cycle variability. Examining the individual THMs by quartile, we found the greatest association with chlorodibromomethane or the sum of the brominated compounds. Incorporating tap water consumption showed a similar pattern of reduced cycle length with increasing TTHM exposure. These findings suggest that THM exposure may affect ovarian function and should be confirmed in other studies.
PMCID: PMC1241528  PMID: 12782495
7.  Blood lead levels and sexual maturation in U.S. girls: the Third National Health and Nutrition Examination Survey, 1988-1994. 
Environmental Health Perspectives  2003;111(5):737-741.
Using data from the Third National Health and Nutrition Examination Survey, we assessed measures of puberty in U.S. girls in relation to blood lead levels to determine whether sexual maturation may be affected by current environmental lead exposure. The study sample included 1,706 girls 8-16 years old with pubic hair and breast development information; 1,235 girls 10-16 years old supplied information on menarche. Blood lead concentrations (range = 0.7-21.7 micro g/dL) were categorized into three levels: 0.7-2.0, 2.1-4.9, and 5.0-21.7 micro g/dL. Sexual maturation markers included self-reported attainment of menarche and physician determined Tanner stage 2 pubic hair and breast development. Girls who had not reached menarche or stage 2 pubic hair had higher blood lead levels than did girls who had. For example, among girls in the three levels of blood lead described above, the unweighted percentages of 10-year-olds who had attained Tanner stage 2 pubic hair were 60.0, 51.2, and 44.4%, respectively, and for girls 12 years old who reported reaching menarche, the values were 68.0, 44.3, and 38.5%, respectively. The negative relation of blood lead levels with attainment of menarche or stage 2 pubic hair remained significant in logistic regression even after adjustment for race/ethnicity, age, family size, residence in metropolitan area, poverty income ratio, and body mass index. In conclusion, higher blood lead levels were significantly associated with delayed attainment of menarche and pubic hair among U.S. girls, but not with breast development.
PMCID: PMC1241484  PMID: 12727603
8.  The National Children's Study of environmental effects on child health and development. 
Environmental Health Perspectives  2003;111(4):642-646.
Increasing recognition that children may be more susceptible than adults to environmental exposures and that they experience potentially life-long consequences of such exposures has led to widespread support for a large new cohort study in the United States. In this article, we propose a framework for a new cohort study of children, with follow-up beginning before birth and continuing to age 21 years. We also describe the administrative structure that has been built to develop the proposal further. The structure includes a partnership between federal and nonfederal scientists and relies on a collaborative, interdisciplinary research effort of unprecedented scale in medical research. We discuss briefly how the proposed cohort could be used to examine, among many other things, the effect of chemical contaminants in breast milk on children's health and development.
PMCID: PMC1241458  PMID: 12676629
9.  Assessing exposure in epidemiologic studies to disinfection by-products in drinking water: report from an international workshop. 
Environmental Health Perspectives  2002;110(Suppl 1):53-60.
The inability to accurately assess exposure has been one of the major shortcomings of epidemiologic studies of disinfection by-products (DBPs) in drinking water. A number of contributing factors include a) limited information on the identity, occurrence, toxicity, and pharmacokinetics of the many DBPs that can be formed from chlorine, chloramine, ozone, and chlorine dioxide disinfection; b) the complex chemical interrelationships between DBPs and other parameters within a municipal water distribution system; and c) difficulties obtaining accurate and reliable information on personal activity and water consumption patterns. In May 2000, an international workshop was held to bring together various disciplines to develop better approaches for measuring DBP exposure for epidemiologic studies. The workshop reached consensus about the clear need to involve relevant disciplines (e.g., chemists, engineers, toxicologists, biostatisticians and epidemiologists) as partners in developing epidemiologic studies of DBPs in drinking water. The workshop concluded that greater collaboration of epidemiologists with water utilities and regulators should be encouraged in order to make regulatory monitoring data more useful for epidemiologic studies. Similarly, exposure classification categories in epidemiologic studies should be chosen to make results useful for regulatory or policy decision making.
PMCID: PMC1241147  PMID: 11834463
10.  Validity and Reliability of the Interval Scale of Anxiety Response 
Anesthesia Progress  1987;34(6):202-206.
The Interval Scale of Anxiety Response (ISAR) is shown to be a valid and reliable instrument for measuring situation dental anxiety in adults. The ISAR demonstrates differences that are known or expected between various population subgroups. Thus, significantly higher scores, indicating greater levels of anxiety, are reported by women compared with men; by hospital clinic patients compared with private practice patients; by occasional compared with regular users of dental care; by those with lower educational levels; and by those patients undergoing exodontia compared with patients having other dental procedures. Younger adults also report significantly higher anxiety scores during treatment than older adults. The ISAR is also significantly associated with other measures of anxiety and pain, and with a measure of dentistrated difficulty of extraction. Reliability is assessed favorably and present-time administration is found to improve ISAR accuracy over its retrospective use.
PMCID: PMC2190041  PMID: 3481516
11.  Development of an Interval Scale of Anxiety Response 
Anesthesia Progress  1986;33(5):220-224.
This paper reports the development of an interval scale of anxiety response. Magnitude estimation procedures were used with three different groups of subjects to develop a suitable scale of seven anxiety descriptors. The ratio of the highest to lowest descriptor magnitudes was 21 to 1. Analyses of the descriptor sets in the various groups indicated high reliability of meaning and high objectivity. In addition, high agreement on meaning was shown for groups of differing education and socioeconomic status. A preliminary study using the scale indicates appropriate preliminary construct validity. Further reliability and validity research is needed. This scale may be useful for assessing anxiety response changes in a variety of contexts.
PMCID: PMC2177487  PMID: 3465256

Results 1-11 (11)