Lynn R. Goldman

Cord Serum Concentrations of Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoate (PFOA) in Relation to Weight and Size at Birth

Background Recent studies have reported developmental toxicity among rodents dosed with perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Objectives We examined the relationship between concentrations of PFOS and PFOA in cord serum (surrogates for in utero exposures) and gestational age, birth weight, and birth size in humans. Methods We conducted a hospital-based cross-sectional epidemiologic study of singleton deliveries in Baltimore, Maryland. Cord serum samples (n = 293) were analyzed for PFOS and PFOA by online solid-phase extraction, coupled with reversed-phase high-performance liquid chromatography–isotope dilution tandem mass spectrometry. Maternal characteristics and anthropometric measures were obtained from medical charts. Results After adjusting for potential confounders, both PFOS and PFOA were negatively associated with birth weight [per ln-unit: β = −69 g, 95% confidence interval (CI), −149 to 10 for PFOS; β = −104 g, 95% CI, −213 to 5 for PFOA], ponderal index (per ln-unit: β = −0.074 g/cm3 × 100, 95% CI, −0.123 to −0.025 for PFOS; β = −0.070 g/cm3 × 100, 95% CI, −0.138 to −0.001 for PFOA), and head circumference (per ln-unit: β = −0.32 cm, 95% CI, −0.56 to −0.07 for PFOS; β = −0.41 cm, 95% CI, −0.76 to −0.07 for PFOA). No associations were observed between either PFOS or PFOA concentrations and newborn length or gestational age. All associations were independent of cord serum lipid concentrations. Conclusions Despite relatively low cord serum concentrations, we observed small negative associations between both PFOS and PFOA concentrations and birth weight and size. Future studies should attempt to replicate these findings in other populations.

Birth delivery mode modifies the associations between prenatal polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels

Background Developing infants may be especially sensitive to hormone disruption from chemicals including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Objective We investigated relationships between cord serum levels of PCBs and PBDEs and thyroid hormones measured in cord blood serum and neonatal blood spots. Methods We measured PCBs and PBDEs, thyrotropin (TSH), thyroxine (T4) and free T4 (FT4) in cord blood serum from 297 infants who were delivered at the Johns Hopkins Hospital in 2004–2005. We abstracted results of total T4 (TT4) measured in blood spots collected in the hospital and at neonatal visits. We used delivery mode (augmented vaginal deliveries and nonelective cesarean deliveries) as a surrogate for intrapartum stress, which is known to alter cord blood thyroid hormones. Results In the full study population, no compounds were associated with a change in average TSH, FT4, or TT4. BDE-100 was associated with increased odds of low cord TT4, BDE-153 with increased odds of low cord TT4 and FT4, and no compounds were associated with increased odds of high TSH. For infants born by spontaneous, vaginal, unassisted deliveries, PCBs were associated with lower cord TT4 and FT4 and lower TT4 measured in neonatal blood spots. PBDEs showed consistent but mainly nonsignificant negative associations with TT4 and FT4 measurements. Conclusions Prenatal PCB and PBDE exposures were associated with reduced TT4 and FT4 levels among infants born by spontaneous, unassisted vaginal delivery. Intrapartum stress associated with delivery mode may mask hormonal effects of PCBs and PBDEs.

Ultraviolet light: A hazard to children

BACKGROUND Sunlight is subdivided into visible light, ranging from 400 nm (violet) to 700 nm (red); longer infrared, “above red” or .700 nm, also called heat; and shorter ultraviolet radiation (UVR), “below violet” or ,400 nm. UVR is further subdivided into UV-A (320–400 nm), also called black (invisible) light; UV-B (290–320 nm), which is more skin-penetrating; and UV-C (,290 nm). UV-B constitutes ,0.5% of sunlight reaching the earth’s surface, but is responsible for most of the acute and chronic sunrelated damage to normal skin.1 Most UVR is absorbed by stratospheric ozone. UV-B has greater intensity in summer than in winter, at midday than in morning or late afternoon, in places closer to the equator, and at high altitudes. Sand, snow, concrete, and water can reflect up to 85% of sunlight, thus intensifying exposure.1

Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds.

Environmental exposures in-utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (>10 ng/ml, mean 123.8 ng/ml), low (range 1-10 ng/ml, mean 1.6 ng/ml) and very low (<1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p<0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean=15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean=29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r= -0.72, p <0.01) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs.

Determinants of Prenatal Exposure to Polychlorinated Biphenyls (PCBs) and Polybrominated Diphenyl Ethers (PBDEs) in an Urban Population

Background Recent studies have reported blood levels of polybrominated diphenyl ethers (PBDEs) in the U.S. population. Information about neonatal levels and about the relationship to polychlorinated biphenyls (PCBs) exposures is limited. Objectives The objective was to characterize levels and determinants of fetal exposure to PBDEs and PCBs among newborns from Baltimore, Maryland. Methods We analyzed umbilical cord blood for eight PBDEs and 35 PCBs from infants delivered at the Johns Hopkins Hospital. Maternal and infant characteristics were abstracted from medical records. Results Ninety-four percent of cord serum samples had quantifiable levels of at least one PBDE congener, and > 99% had at least one detectable PCB congener. PBDE concentrations in cord blood were similar to those reported in other studies from North America. Strong correlations were observed within but not across PCB and PBDE classes. Multivariate models showed that many factors independently predicted exposure to BDE-47, BDE-100, and BDE-153 and CB-118, CB-138/158, CB-153, and CB-180. Generally, infants of Asian mothers had lower PBDE and PCB levels, and infants of smokers had higher levels. Increased maternal body mass index was associated with lower levels of PCBs but not PBDEs. Levels of PCBs but not PBDEs were lower in births from married and multiparous mothers. Increased maternal age was associated with higher PCB levels but lower PBDE levels. Conclusions Although many of the factors we investigated were independent predictors of both PBDE and PCB levels, in some cases the direction of associations was different. More research is needed to better understand the sources and pathways of PBDE exposure.

Children’s Vulnerability To Toxic Chemicals: A Challenge And Opportunity To Strengthen Health And Environmental Policy

A key policy breakthrough occurred nearly twenty years ago with the discovery that children are far more sensitive than adults to toxic chemicals in the environment. This finding led to the recognition that chemical exposures early in life are significant and preventable causes of disease in children and adults. We review this knowledge and recommend a new policy to regulate industrial and consumer chemicals that will protect the health of children and all Americans, prevent disease, and reduce health care costs. The linchpins of a new US chemical policy will be: first, a legally mandated requirement to test the toxicity of chemicals already in commerce, prioritizing chemicals in the widest use, and incorporating new assessment technologies; second, a tiered approach to premarket evaluation of new chemicals; and third, epidemiologic monitoring and focused health studies of exposed populations.

Children - unique and vulnerable. Environmental risks facing children and recommendations for response

Children may be more susceptible to exposures to environmental toxins than adults and may be more vulnerable to their effects. Because of this, the health care community and those responsible for children need to be alert to possible environmental factors in identifying and responding to the health problems of children. Their focus should be on the causes of the health problem, emphasizing environmental sources, and not on simply treating the symptoms.

Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model—Recommendations From an NIH Workshop

Although it is recognized that many common complex diseases are a result of multiple genetic and environmental risk factors, studies of gene‐environment interaction remain a challenge and have had limited success to date. Given the current state‐of‐the‐science, NIH sought input on ways to accelerate investigations of gene‐environment interplay in health and disease by inviting experts from a variety of disciplines to give advice about the future direction of gene‐environment interaction studies. Participants of the NIH Gene‐Environment Interplay Workshop agreed that there is a need for continued emphasis on studies of the interplay between genetic and environmental factors in disease and that studies need to be designed around a multifaceted approach to reflect differences in diseases, exposure attributes, and pertinent stages of human development. The participants indicated that both targeted and agnostic approaches have strengths and weaknesses for evaluating main effects of genetic and environmental factors and their interactions. The unique perspectives represented at the workshop allowed the exploration of diverse study designs and analytical strategies, and conveyed the need for an interdisciplinary approach including data sharing, and data harmonization to fully explore gene‐environment interactions. Further, participants also emphasized the continued need for high‐quality measures of environmental exposures and new genomic technologies in ongoing and new studies. Genet. Epidemiol. 35: 217‐225, 2011.  © 2011 Wiley‐Liss, Inc.

Misuse of blood serum to assess exposure to bisphenol A and phthalates

We noted serious methodologic issues in the measurement of bisphenol A (BPA), phthalate diesters, and their metabolites in blood serum and other tissues, as reported in the recent Breast Cancer Research article by Sprague and colleagues [1]. Such measurements are analytically possible. However, for the reasons that follow, it is seldom possible to verify that serum concentrations of these compounds are valid measures of exposure. BPA and phthalate diesters are non-persistent in the body; they metabolize quickly and, as a result, the levels of their polar, hydrophilic metabolites in blood can be several orders of magnitude lower than in urine (controlled human studies suggest 30- to 100-fold higher levels in urine than serum) [2-4]. Such low levels increase the possibility that contamination can obscure true exposures. Extraneous sources of phthalate diesters include plastics, personal care and consumer products, and building furnishings [2,5]. Phthalate diesters derived externally can easily contaminate blood serum and other human matrices and overwhelm the very low levels in blood from daily exposures [2,4]. Hydrolytic enzymes are ubiquitous in blood and most other matrices (but not urine). These enzymes rapidly hydrolyze extraneous phthalate diesters to their corresponding monoesters, beginning immediately after sample collection, and this can artificially elevate the concentrations of these hydrolytic monoesters, including monoethyl phthalate and mono-(2-ethylhexyl) phthalate. To the best of our knowledge, phthalate oxidative metabolites (such as mono-(2-ethyl-5-oxohexyl) phthalate) do not form as a result of recent external contamination. The oxidative metabolites were not measured in the study by Sprague and colleagues [1]. Therefore, in blood, saliva, or tissues other than urine, only the phthalate oxidative metabolites (not the phthalate diesters or the hydrolytic monoesters) are valid exposure biomarkers. BPA also has extraneous sources such as plastics [3,5]. There are currently no comparable oxidative metabolites that can exclude recent contamination, but conjugated BPA (not ‘free’ BPA) is the most valid exposure biomarker and is not present to any significant degree in biological samples other than urine. For these reasons, urine is the best matrix for epidemiological assessment of exposure to BPA, phthalates, and other polar, non-persistent chemicals to whose exposures can be episodic in nature. Moreover, because both BPA and the phthalate diesters have very short half-lives (regardless of the biomarker used), great care must be taken to ensure that measurements represent the daily habits of research subjects versus brief exposures from iatrogenic sources, such as collection devices, clinical apparatus, and tubing from medical procedures [2,5].

Aldicarb food poisonings in California, 1985-1988: toxicity estimates for humans.

Three outbreaks of food poisoning involving watermelons or cucumbers and caused by the carbamate pesticide aldicarb occurred in California between 1985 and 1988. For each outbreak, and for an outbreak of aldicarb poisoning associated with English cucumbers previously reported in the literature, dosages of aldicarb sulfoxide that caused the illnesses were estimated. Estimated dosages ranged between 0.0023 [corrected] and 0.06 mg/kg body weight, and most were well below the 0.025 mg/kg Lowest Observed Effect Level (LOEL) for subclinical blood cholinesterase depression previously reported for humans. These findings are consistent with aldicarb sulfoxide (ASO) illnesses that have occurred in other states. Aldicarb appears to be more toxic than previously suspected. Scientific and regulatory implications are discussed.