Biomonitoring of populations in Western New York at risk for exposure to Great Lakes contaminants.

The New York State Department of Health conducted the Healthy Fishing Communities Program in collaboration with the Agency for Toxic Substances and Disease Registry to assess human exposure to contaminants common to Lake Ontario, Lake Erie and surrounding rivers and waterways among populations in western New York State who eat locally caught fish. The program enrolled licensed anglers and Burmese refugees and immigrants, living near four designated Great Lakes Areas of Concern: Buffalo River, Niagara River, Eighteenmile Creek, and the Rochester Embayment. These target populations were sampled and enrolled independently into the program between February and October of 2013. A core set of contaminants were measured in blood and urine of 409 licensed anglers and 206 Burmese refugees and immigrants which included lead, cadmium, mercury, PCBs, PBDEs, organochlorine pesticides (hexachlorobenzene, mirex, DDT, DDE, and chlordane and its metabolites oxychlordane and trans-Nonachlor), and PFOS and PFOA. Biomonitoring results showed that both groups had higher geometric means for blood lead, total blood mercury, and serum PFOS compared to the 2013-2014 NHANES reference levels. The Burmese refugee group also showed higher geometric means for creatinine-adjusted urine mercury and lipid-adjusted serum DDE compared to national levels. Licensed angler participants reported eating a median of 16 locally caught fish meals in the past year. Burmese participants consumed local fish throughout the year, and most frequently in the summer (median 39 fish meals or 3 times a week). The study results provide valuable information on populations at high risk of exposure to contaminants in the Great Lakes Basin of western New York. The results provide the foundation for developing and implementing public health actions to reduce potential exposures to Great Lakes pollutants.

Tracking Declines in Mercury Exposure in the New York City Adult Population, 2004-2014.

Mercury is a toxic metal that can be measured in human blood and urine. Population-based biomonitoring from 2004 guided New York City (NYC) Department of Health and Mental Hygiene (DOHMH) efforts to reduce exposures by educating the public about risks and benefits of fish consumption-a predominant source of exposure in the general population-and removing mercury-containing skin-lightening creams and other consumer products from the marketplace. We describe changes in exposures over the past decade in relation to these local public health actions and in the context of national changes by comparing mercury concentrations measured in blood (1201 specimens) and urine (1408 specimens) from the NYC Health and Nutrition Examination Survey (NYC HANES) 2013-2014 with measurements from NYC HANES 2004 and National Health and Nutrition Examination Surveys (NHANES) 2003-2004 and 2013-2014. We found that NYC adult blood and urine geometric mean mercury concentrations decreased 46% and 45%, respectively. Adult New Yorkers with blood mercury concentration ≥ 5 µg/L (the New York State reportable level) declined from 24.8% (95% CL = 22.2%, 27.7%) to 12.0% (95% CL = 10.1%, 14.3%). The decline in blood mercury in NYC was greater than the national decline, while the decline in urine mercury was similar. As in 2004, Asian New Yorkers had higher blood mercury concentrations than other racial/ethnic groups. Foreign-born adults of East or Southeast Asian origin had the highest prevalence of reportable levels (29.7%; 95% CL = 21.0%, 40.1%) across sociodemographic groups, and Asians generally were the most frequent fish consumers, eating on average 11 fish meals in the past month compared with 7 among other groups (p < 0.001). Fish consumption patterns were similar over time, and fish continues to be consumed more frequently in NYC than nationwide (24.7% of NYC adults ate fish ten or more times in the past 30 days vs. 14.7% nationally, p < 0.001). The findings are consistent with the hypothesis that blood mercury levels have declined in part because of local and national efforts to promote consumption of lower mercury fish. Local NYC efforts may have accelerated the reduction in exposure. Having "silver-colored fillings" on five or more teeth was associated with the highest 95th percentile for urine mercury (4.06 µg/L; 95% CL = 3.1, 5.9). An estimated 5.5% of the adult population (95% CL = 4.3%, 7.0%) reported using a skin-lightening cream in the past 30 days, but there was little evidence that use was associated with elevated urine mercury in 2013-14.

Low-level environmental metals and metalloids and incident pregnancy loss.

Environmental exposure to metals and metalloids is associated with pregnancy loss in some but not all studies. We assessed arsenic, cadmium, mercury, and lead concentrations in 501 couples upon trying for pregnancy and followed them throughout pregnancy to estimate the risk of incident pregnancy loss. Using Cox proportional hazard models, we estimated hazard ratios (HR) and 95% confidence intervals (CIs) for pregnancy loss after covariate adjustment for each partner modeled individually then we jointly modeled both partners' concentrations. Incidence of pregnancy loss was 28%. In individual partner models, the highest adjusted HRs were observed for female and male blood cadmium (HR=1.08; CI 0.81, 1.44; HR=1.09; 95% CI 0.84, 1.41, respectively). In couple based models, neither partner's blood cadmium concentrations were associated with loss (HR=1.01; 95% CI 0.75, 1.37; HR=0.92; CI 0.68, 1.25, respectively). We observed no evidence of a significant relation between metal(loids) at these environmentally relevant concentrations and pregnancy loss.

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study.

PURPOSE: A hypothesis-generating pilot study exploring associations between essential trace elements measured in follicular fluid (FF) and urine and in vitro fertilization (IVF) endpoints. METHODS: We recruited 58 women undergoing IVF between 2007 and 2008, and measured cobalt, chromium, copper, manganese, molybdenum, and zinc in FF (n = 46) and urine (n = 45) by inductively coupled plasma mass spectrometry (ICP-MS). We used multivariable regression models to assess the impact of FF and urine trace elements on IVF outcomes, adjusted for age, body mass index, race, and cigarette smoking. RESULTS: Trace elements were mostly present at lower concentrations in FF than in urine. The average number of oocytes retrieved was positively associated with higher urine cobalt, chromium, copper, and molybdenum concentrations. FF chromium and manganese were negatively associated with the proportion of mature oocytes, yet urine manganese had a positive association. FF zinc was inversely associated with average oocyte fertilization. Urine trace elements were significant positive predictors for the total number of embryos generated. FF copper predicted lower embryo fragmentation while urine copper was associated with higher embryo cell number and urine manganese with higher embryo fragmentation. No associations were detected for implantation, pregnancy, or live birth. CONCLUSIONS: Our results suggest the importance of trace elements in both FF and urine for intermediate, although not necessarily clinical, IVF endpoints. The results differed using FF or urine biomarkers of exposure, which may have implications for the design of clinical and epidemiologic investigations. These initial findings will form the basis of a more definitive future study.

Birth outcomes and background exposures to select elements, the Longitudinal Investigation of Fertility and the Environment (LIFE).

Evidence suggests that trace exposures to select elements may increase the risk for adverse birth outcomes. To investigate further, we used multiple regression to assess associations between preconception parental exposures to Pb, Cd, and total Hg in blood, and 21 elements in urine, with n=235 singleton birth outcomes, adjusted for confounders and partner's exposure. Earlier gestational age at delivery (GA) was associated with higher tertiles of urine maternal W (-1.22 days) and paternal U (-1.07 days), but GA was later for higher tertiles of maternal (+1.11 days) and paternal (+1.30 days) blood Hg. Additional analysis indicated shorter GA associated with higher paternal urine Ba, W, and U, and with higher maternal blood Pb for boys, but GA was longer in association with higher maternal urine Cr. Birth weight (BW) was lower for higher tertiles of paternal urine Cs (-237.85g), U (-187.34g), and Zn (-209.08g), and for higher continuous Cr (P=0.021). In contrast, BW was higher for higher tertiles of paternal urine As (+194.71g) and counterintuitively for maternal blood Cd (+178.52g). Birth length (BL) was shorter for higher tertiles of urine maternal W (-1.22cm) and paternal U (-1.10cm). Yet, higher tertiles of maternal (+1.11cm) and paternal (+1.30) blood Hg were associated with longer BL. Head circumference at delivery was lower for higher tertiles of paternal urine U (-0.83cm), and for higher continuous Mo in boys (-0.57cm). Overall, associations were most consistently indicated for GA and measures of birth size with urine W and U, and paternal exposures were more frequently associated than maternal. Though limited by several factors, ours is the largest multi-element investigation of prospective couple-level trace exposures and birth outcomes to date; the novel observations for W and U merit further investigation.

Urine cortisol concentration as a biomarker of stress is unrelated to IVF outcomes in women and men.

PURPOSE: Our primary objective was to assess associations between urine cortisol as a biomarker of psychological stress and in vitro fertilization (IVF) outcomes. A secondary objective was to assess associations between toxic metals and cortisol. METHODS: Urine and blood specimens were collected from 52 women and 28 male partners completing a first IVF procedure, on the day of oocyte retrieval. Urine cortisol was measured with an enzyme-linked immunosorbent assay. Mercury (Hg), cadmium (Cd), and lead (Pb) were determined in blood and Cd in urine by inductively coupled plasma-mass spectrometry. RESULTS: No associations were indicated for cortisol with IVF outcomes in multivariable regression models adjusted for covariates. However, we detected positive linear associations for cortisol and urine Cd (ß = 9.96, 95%CI 1.52, 21.44) and blood Hg (ß = 1.44, 95%CI 0.31, 3.18). An exploratory stratified analysis suggested a potential inverse association between urine cortisol and oocyte fertilization among women with low, but not high blood Hg. CONCLUSION: While limited, these preliminary data suggest that psychological stress may not play a major role in IVF outcomes, which therefore could be one less concern for couples and their clinicians. Our data also raise the possibility for toxic metals to modify associations between cortisol and IVF outcomes among women. However, these preliminary results require corroboration in an experimental animal model and confirmation in a larger, more definitive observational study.

Association of arsenic and metals with concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D among adolescents in Torreón, Mexico.

BACKGROUND: Limited data suggest that lead (Pb), cadmium (Cd), and uranium (U) may disrupt vitamin D metabolism and inhibit production of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active vitamin D metabolite, from 25-hydroxyvitamin D [25(OH)D] in the kidney. OBJECTIVES: We evaluated the association between blood lead (BPb) and urine arsenic (As), Cd, molybdenum (Mo), thallium (Tl), and U with markers of vitamin D metabolism [25(OH)D and 1,25(OH)2D]. METHODS: We conducted a cross-sectional study of 512 adolescents in Torreón, a town in Mexico with a Pb smelter near residential areas. BPb was measured using atomic absorption spectrometry. Urine As, Cd, Mo, Tl, and U were measured using inductively coupled plasma mass spectrometry. Serum 25(OH)D and 1,25(OH)2D were measured using a chemiluminescent immunoassay and a radioimmunoassay, respectively. Multivariable linear models with vitamin D markers as the outcome were used to estimate associations of BPb and creatinine-corrected urine As and metal concentrations with serum vitamin D concentrations, controlling for age, sex, adiposity, smoking, socioeconomic status, and time outdoors. RESULTS: Serum 25(OH)D was positively associated with urine Mo and Tl [1.5 (95% CI: 0.4, 2.6) and 1.2 (95% CI: 0.3, 2.1) ng/mL higher with a doubling of exposure, respectively]. Serum 1,25(OH)2D was positively associated with urine As and U [3.4 (95% CI: 0.9, 5.9) and 2.2 (95% CI: 0.7, 3.7) pg/mL higher, respectively], with little change in associations after additional adjustment for serum 25(OH)D. Pb and Cd were not associated with 25(OH)D or 1,25(OH)2D concentrations. CONCLUSIONS: Overall, our findings did not support a negative effect of As or metal exposures on serum 1,25(OH)2D concentrations. Additional research is needed to confirm positive associations between serum 1,25(OH)2D and urine U and As concentrations and to clarify potential underlying mechanisms.

Maternal mercury exposure, season of conception and adverse birth outcomes in an urban immigrant community in Brooklyn, New York, U.S.A.

Adverse birth outcomes including preterm birth (PTB: <37 weeks gestation) and low birth weight (LBW: <2500 g) can result in severe infant morbidity and mortality. In the United States, there are racial and ethnic differences in the prevalence of PTB and LBW. We investigated the association between PTB and LBW with prenatal mercury (Hg) exposure and season of conception in an urban immigrant community in Brooklyn, New York. We recruited 191 pregnant women aged 18-45 in a Brooklyn Prenatal Clinic and followed them until delivery. Urine specimens were collected from the participants during the 6th to 9th month of pregnancy. Cord blood specimens and neonate anthropometric data were collected at birth. We used multivariate logistic regression models to investigate the odds of LBW or PTB with either maternal urinary mercury or neonate cord blood mercury. We used linear regression models to investigate the association between continuous anthropometric outcomes and maternal urinary mercury or neonate cord blood mercury. We also examined the association between LBW and PTB and the season that pregnancy began. Results showed higher rates of PTB and LBW in this cohort of women compared to other studies. Pregnancies beginning in winter (December, January, February) were at increased odds of LBW births compared with births from pregnancies that began in all other months (OR7.52 [95% CI 1.65, 34.29]). We observed no association between maternal exposure to Hg, and either LBW or PTB. The apparent lack of association is consistent with other studies. Further examination of seasonal association with LBW is warranted.

Increased urinary cobalt and whole blood concentrations of cadmium and lead in women with uterine leiomyomata: Findings from the ENDO Study.

Multiple trace elements have estrogen receptor activity, but the association of these elements with uterine leiomyoma has not been defined. A cohort of 473 women aged 18-44 undergoing surgery for benign gynecologic indications provided whole blood and urine specimens for trace element analysis, which was performed by inductively coupled plasma mass spectrometry. Twenty elements were analyzed in blood and 3 in urine. The surgeon documented whether fibroids were present. Geometric mean concentrations were compared between women with and without fibroids, and logistic regression models were generated to assess the impact of the concentration of each trace element on the odds of fibroids. In multivariate regressions, odds of a fibroid diagnosis were higher with increased whole blood cadmium (AOR 1.44, 95% CI 1.02, 2.04) and lead (AOR 1.31 95% CI 1.02, 1.69), and urine cobalt (AOR 1.31, 95% CI 1.02, 1.70). Urinary cadmium and lead were not related to fibroid diagnosis. Increased exposure to trace elements may contribute to fibroid growth, and fibroids may serve as a reservoir for these elements. Differences between urinary and whole blood findings merit further investigation, as urinary cadmium has been considered a superior marker of exposure.

Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents.

Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 µg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (ß coefficient=3.1 mL/min/1.73 m(2); 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary.

Regional distribution and accumulation of lead in caprine brain tissues following a long-term oral dosing regimen.

It is well known that the brain is a key target organ for lead (Pb)-induced toxicity, with exposure potentially resulting in numerous adverse neurological effects. However, information on the distribution and accumulation of Pb within different brain regions is scarce. In this study, Pb uptake and accumulation were characterized in brain and related tissues obtained from a convenience sample of goats dosed with Pb. Tissues were harvested postmortem from 10 animals (9 dosed and 1 undosed) that are used to produce blood Pb pools for the New York State Department of Health's Proficiency Testing program. Whole brains were subdivided into 14 distinct anatomical regions to explore interregional differences. Related tissues included the olfactory epithelium and spinal cord. Where sufficient tissue mass permitted, further subdivision into smaller sections was carried out to examine intraregional Pb variability. Determination of Pb content in these tissues was accomplished using inductively coupled plasma mass spectrometry (ICP-MS), with accuracy assessed using reference materials certified for Pb. Lead content (dry weight) varied from <10 ng/g, that is, below the method detection limit, to as much as 4.45 × 10(4) ng/g Pb. Olfactory epithelium Pb content was several orders of magnitude greater than found in other regions analyzed. Enrichment of Pb was also observed in the olfactory bulb and choroid plexus. Data for each region analyzed were pooled from all goats to identify regions with the greatest propensity for Pb accumulation. Data related to Pb content were also assessed individually within each goat and significant differences in Pb content between regions were determined.

Spatial clustering of toxic trace elements in adolescents around the Torreón, Mexico lead-zinc smelter.

High blood lead (BPb) levels in children and elevated soil and dust arsenic, cadmium, and lead were previously found in Torreón, northern Mexico, host to the world's fourth largest lead-zinc metal smelter. The objectives of this study were to determine spatial distributions of adolescents with higher BPb and creatinine-corrected urine total arsenic, cadmium, molybdenum, thallium, and uranium around the smelter. Cross-sectional study of 512 male and female subjects 12-15 years of age was conducted. We measured BPb by graphite furnace atomic absorption spectrometry and urine trace elements by inductively coupled plasma-mass spectrometry, with dynamic reaction cell mode for arsenic. We constructed multiple regression models including sociodemographic variables and adjusted for subject residence spatial correlation with spatial lag or error terms. We applied local indicators of spatial association statistics to model residuals to identify hot spots of significant spatial clusters of subjects with higher trace elements. We found spatial clusters of subjects with elevated BPb (range 3.6-14.7 µg/dl) and urine cadmium (0.18-1.14 µg/g creatinine) adjacent to and downwind of the smelter and elevated urine thallium (0.28-0.93 µg/g creatinine) and uranium (0.07-0.13 µg/g creatinine) near ore transport routes, former waste, and industrial discharge sites. The conclusion derived from this study was that spatial clustering of adolescents with high BPb and urine cadmium adjacent to and downwind of the smelter and residual waste pile, areas identified over a decade ago with high lead and cadmium in soil and dust, suggests that past and/or present plant operations continue to present health risks to children in those neighborhoods.

Certification of Total Arsenic in Blood and Urine Standard Reference Materials by Radiochemical Neutron Activation Analysis and Inductively Coupled Plasma - Mass Spectrometry.

A newly developed procedure for determination of arsenic by radiochemical neutron activation analysis (RNAA) was used to measure arsenic at four levels in SRM 955c Toxic Elements in Caprine Blood and at two levels in SRM 2668 Toxic Elements in Frozen Human Urine for the purpose of providing mass concentration values for certification. Samples were freeze-dried prior to analysis followed by neutron irradiation for 3 h at a fluence rate of 1×1014cm-2s-1. After sample dissolution in perchloric and nitric acids, arsenic was separated from the matrix by extraction into zinc diethyldithiocarbamate in chloroform, and 76As quantified by gamma-ray spectroscopy. Differences in chemical yield and counting geometry between samples and standards were monitored by measuring the count rate of a 77As tracer added before sample dissolution. RNAA results were combined with inductively coupled plasma - mass spectrometry (ICP-MS) values from NIST and collaborating laboratories to provide certified values of (10.81 ± 0.54) µg/kg and (213.1 ± 0.73) µg/kg for SRM 2668 Levels I and II, and certified values of (21.66 ± 0.73) µg/kg, (52.7 ± 1.1) µg/kg, and (78.8 ± 4.9) µg/kg for SRM 955c Levels 2, 3, and 4 respectively. Because of discrepancies between values obtained by different methods for SRM 955c Level 1, an information value of < 5 µg/kg was assigned for this material.

Uranium associations with kidney outcomes vary by urine concentration adjustment method.

Uranium is a ubiquitous metal that is nephrotoxic at high doses. Few epidemiologic studies have examined the kidney filtration impact of chronic environmental exposure. In 684 lead workers environmentally exposed to uranium, multiple linear regression was used to examine associations of uranium measured in a 4-h urine collection with measured creatinine clearance, serum creatinine- and cystatin-C-based estimated glomerular filtration rates, and N-acetyl-ß-D-glucosaminidase (NAG). Three methods were utilized, in separate models, to adjust uranium levels for urine concentration--µg uranium/g creatinine; µg uranium/l and urine creatinine as separate covariates; and µg uranium/4 h. Median urine uranium levels were 0.07 µg/g creatinine and 0.02 µg/4 h and were highly correlated (rs=0.95). After adjustment, higher ln-urine uranium was associated with lower measured creatinine clearance and higher NAG in models that used urine creatinine to adjust for urine concentration but not in models that used total uranium excreted (µg/4 h). These results suggest that, in some instances, associations between urine toxicants and kidney outcomes may be statistical, due to the use of urine creatinine in both exposure and outcome metrics, rather than nephrotoxic. These findings support consideration of non-creatinine-based methods of adjustment for urine concentration in nephrotoxicant research.

Trace elements and endometriosis: the ENDO study.

There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.

A pilot study of seafood consumption and exposure to mercury, lead, cadmium and arsenic among infertile couples undergoing in vitro fertilization (IVF).

This cross-sectional pilot study was conducted to assess environmental exposures to toxic elements through seafood consumption, among infertile couples undergoing in vitro fertilization (IVF). Twenty-five women and 15 men completed a questionnaire, and provided biologic specimens for quantification of Hg, Pb, Cd, and As using ICP-MS. Consumption of 'mollusks' and 'shellfish' are associated with increased blood Hg. Other seafood consumption predicts blood Pb, and urine Cd and As. Though limited by small numbers and the cross-sectional design, these results suggest that consumption of specific seafood items increases exposure to toxic elements in couples undergoing IVF.

Trace element analysis of human urine collected after administration of Gd-based MRI contrast agents: characterizing spectral interferences using inorganic mass spectrometry.

Analysis of human urine is commonly used in biomonitoring studies to assess exposure to essential (e.g., Cu, Zn, Se) and non-essential (Pb, Cd, Pt) trace elements. These data are also used in epidemiological studies to evaluate potential associations between trace element exposure and various health outcomes within a population. Today most trace element analyses are typically performed using quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS). However, there is always the potential for spectral interferences with Q-ICP-MS instrumentation, especially when analyzing human specimens that may contain medications and other exogenous substances. Moreover, such xenobiotics may be unknown to the investigators. In a recent study focusing on environmental exposures and endometriosis: Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO Study), urine specimens (n=619) were collected from participating women upon enrollment into the study or prior to surgery or pelvic magnetic resonance imaging (MRI), and analyzed for 21 trace elements by Q-ICP-MS. Here we report on some anomalous results observed for Se and Pt with elevated concentrations up to several orders of magnitude greater than what might be expected based on established reference intervals. Further investigations using Sector Field (SF-) ICP-MS instrumentation led to identification of doubly charged and polyatomic gadolinium (Gd) species traced to a Gd-based contrast agent that was administered to some subjects just prior to urine collection. Specifically, interferences from Gd2+ and several minor polyatomics were identified as interferences on all of the major isotopes of Se including 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se. While trace amounts of Pt were present in the urine, a number of Gd-containing polyatomic species were also evident as major interferences on all isotopes of Pt (190Pt, 192Pt, 194Pt, 195Pt, 196Pt, and 198Pt), including Gd-chlorides, Gd-argides, and Gd-oxides. These observations underscore the importance of considering potential isobaric interferences when interpreting unusual trace element results for clinical specimens.

Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes.

PURPOSE: We previously reported associations between trace concentrations of Hg, Cd and Pb in blood and urine and reproductive outcomes for women undergoing in-vitro fertilization (IVF). Here we assess measurements in single follicular fluid (FF) specimens from 46 women as a presumably more relevant marker of dose for reproductive toxicity. METHODS: FF specimens were analyzed for Hg, Cd and Pb using sector field-inductively coupled plasma-mass spectrometry (SF-ICP-MS). Variability sources were assessed by nested ANOVA. Multivariable regression was used to evaluate associations for square root transformed metals with IVF outcomes, adjusting for confounders. RESULTS: An inverse association is detected for FF Pb and fertilization (relative risk (RR) = 0.68, P = 0.026), although positive for Cd (RR = 9.05, P = 0.025). While no other statistically significant associations are detected, odds ratios (OR) are increased for embryo cleavage with Hg (OR = 3.83, P = 0.264) and Cd (OR = 3.18, P = 0.644), and for embryo fragmentation with Cd (OR = 4.08, P = 0.586) and Pb (OR = 2.22, P = 0.220). Positive estimates are observed for Cd with biochemical (RR = 19.02, P = 0.286) and clinical pregnancies (RR = 38.80, P = 0.212), yet with very low precision. CONCLUSIONS: We have identified associations between trace amounts of Pb and Cd in FF from a single follicle, and oocyte fertilization. Yet, the likelihood of biological variation in trace element concentrations within and between follicles, coupled with levels that are near the limits of detection suggest that future work should examine multiple follicles using a 'one follicle-one oocyte/embryo' approach. A larger study is merited to assess more definitively the role that these environmental factors could play with respect to egg quality in IVF programs.

Background exposure to toxic metals in women adversely influences pregnancy during in vitro fertilization (IVF).

Low-level environmental exposure to Hg, Pb and Cd may interfere with pregnancy during in vitro fertilization (IVF). The aim of this study was to generate hypotheses concerning associations between background exposures and pregnancy. In modified Poisson regression models including 24 women and adjusted for urine Cd and creatinine, blood Pb, age, race and smoking, 1 µg/L increases in blood Hg are associated with decreases of 35% (P=0.03) and 33% (P=0.01) in clinical and biochemical pregnancies, respectively. In alternate Poisson models including 26 women and adjusted for blood Pb, blood Hg, age, race and smoking, 1 µg/L increases in blood Cd are associated with decreases of 94% (P=0.01) and 82% (P=0.04) in clinical and biochemical pregnancies, respectively. No effects are detected in 15 men, although inverse associations are suggested for urine cadmium and pregnancy. These data suggest that low-level, background exposures to Hg and Cd may interfere with pregnancy following IVF.