John Osterloh

Hair Mercury Levels in U.S. Children and Women of Childbearing Age: Reference Range Data from NHANES 1999–2000

Exposure to methyl mercury, a risk factor for neurodevelopmental toxicity, was assessed in U.S. children 1–5 years of age (n = 838) and women 16–49 years of age (n = 1,726) using hair mercury analysis during the 1999–2000 National Health and Nutrition Examination Survey (NHANES). The data are nationally representative and are based on analysis of cross-sectional data for the non-institutionalized, U.S. household population. The survey consisted of interviews conducted in participants’ homes and standardized health examinations conducted in mobile examination centers. Distributions of total hair mercury levels expressed as micrograms per gram hair Hg and the association of hair Hg levels with sociodemographic characteristics and fish consumption are reported. Geometric mean (standard error of the geometric mean) hair mercury was 0.12 μg/g (0.01 μg/g) in children, and 0.20 μg/g (0.02 μg/g) in women. Among frequent fish consumers, geometric mean hair mercury levels were 3-fold higher for women (0.38 vs. 0.11 μg/g) and 2-fold higher for children (0.16 vs. 0.08 μg/g) compared with nonconsumers. The NHANES 1999–2000 data provide population-based data on hair mercury concentrations for women and children in the United States. Hair mercury levels were associated with age and fish consumption frequency.

Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States.

Background Perchlorate is commonly found in the environment and known to inhibit thyroid function at high doses. Assessing the potential effect of low-level exposure to perchlorate on thyroid function is an area of ongoing research. Objectives We evaluated the potential relationship between urinary levels of perchlorate and serum levels of thyroid stimulating hormone (TSH) and total thyroxine (T4) in 2,299 men and women, ≥ 12 years of age, participating in the National Health and Nutrition Examination Survey (NHANES) during 2001–2002. Methods We used multiple regression models of T4 and TSH that included perchlorate and covariates known to be or likely to be associated with T4 or TSH levels: age, race/ethnicity, body mass index, estrogen use, menopausal status, pregnancy status, premenarche status, serum C-reactive protein, serum albumin, serum cotinine, hours of fasting, urinary thiocyanate, urinary nitrate, and selected medication groups. Results Perchlorate was not a significant predictor of T4 or TSH levels in men. For women overall, perchlorate was a significant predictor of both T4 and TSH. For women with urinary iodine < 100 μg/L, perchlorate was a significant negative predictor of T4 (p < 0.0001) and a positive predictor of TSH (p = 0.001). For women with urinary iodine ≥ 100 μg/L, perchlorate was a significant positive predictor of TSH (p = 0.025) but not T4 (p = 0.550). Conclusions These associations of perchlorate with T4 and TSH are coherent in direction and independent of other variables known to affect thyroid function, but are present at perchlorate exposure levels that were unanticipated based on previous studies.

Perchlorate Exposure of the US Population, 2001-2002

Perchlorate is commonly found in the environment and can impair thyroid function at pharmacological doses. As a result of the potential for widespread human exposure to this biologically active chemical, we assessed perchlorate exposure in a nationally representative population of 2820 US residents, ages 6 years and older, during 2001 and 2002 as part of the National Health and Nutrition Examination Survey (NHANES). We found detectable levels of perchlorate (>0.05 μg/l) in all 2820 urine samples tested, indicating widespread human exposure to perchlorate. Urinary perchlorate levels were distributed in a log normal fashion with a median of 3.6 μg/l (3.38 μg/g creatinine) and a 95th percentile of 14 μg/l (12.7 μg/g creatinine). When geometric means of urinary perchlorate levels were adjusted for age, fasting, sex and race-ethnicity, we found significantly higher levels of urinary perchlorate in children compared with adolescents and adults. We estimated total daily perchlorate dose for each adult (ages 20 years and older), based on urinary perchlorate, urinary creatinine concentration and physiological parameters predictive of creatinine excretion rate. The 95th percentile of the distribution of estimated daily perchlorate doses in the adult population was 0.234 μg/kg-day [CI 0.202–0.268 μg/kg-day] and is below the EPA reference dose (0.7 μg/kg-day), a dose estimated to be without appreciable risk of adverse effects during a lifetime of exposure. These data provide the first population-based assessment of the magnitude and prevalence of perchlorate exposure in the US.

HYDROXOCOBALAMIN AS A CYANIDE ANTIDOTE: SAFETY, EFFICACY AND PHARMACOKINETICS IN HEAVILY SMOKING NORMAL VOLUNTEERS

The safety, efficacy and pharmacokinetic parameters of 5 g of hydroxocobalamin given intravenously, alone or in combination with 12.5 g of sodium thiosulfate, were evaluated in healthy adult men who were heavy smokers. Sodium thiosulfate caused nausea, vomiting, and localized burning, muscle cramping, or twitching at the infusion site. Hydroxocobalamin was associated with a transient reddish discoloration of the skin, mucous membranes, and urine, and when administered alone produced mean elevations of 13.6% in systolic and 25.9% in diastolic blood pressure, with a concomitant 16.3% decrease in heart rate. No other clinically significant adverse effects were noted. Hydroxocobalamin alone decreased whole blood cyanide levels by 59% and increased urinary cyanide excretion. Pharmacokinetic parameters of hydroxocobalamin were best defined in the group who received both antidotes: t1/2 (alpha), 0.52 h; t1/2 (beta), 2.83 h; Vd (beta), 0.24 L/kg; and mean peak serum concentration 753 mcg/mL (560 mumol/L) at 0-50 minutes after completion of infusion. Hydroxocobalamin is safe when administered in a 5 gram intravenous dose, and effectively decreases the low whole blood cyanide levels found in heavy smokers.

Serum Formate Concentrations in Methanol Intoxication as a Criterion for Hemodialysis

To evaluate the utility of serum formate concentrations, four patients were studied after ingestion of a methanolic copying fluid. All patients were initially intoxicated. Twelve to twenty-four hours later, signs and symptoms included nausea, abdominal pain, hypokalemia, acidosis (three patients), and pathologic ocular findings (two patients). All patients were treated with ethanol and folate. The two patients with ocular signs and acidosis had high serum formate concentrations (75 and 55 mg/dL, respectively). One of the two patients had a high methanol concentration (222 mg/dL) and required hemodialysis; the other patient did not (methanol concentration, 24 mg/dL). In the other two patients without ocular signs, initial formate concentrations were undetectable (limit of detection, 0.5 mg/dL); however, one patient required hemodialysis because the methanol concentration was 72 mg/dL. Formate is the mediator of ocular injury and acidosis. In these patients formate concentrations correlated with the clinical condition but methanol concentrations did not.

Total blood mercury concentrations in the U.S. population: 1999-2006

We describe the distribution and demographic characteristics of total blood Hg levels in the U.S. general population among persons ages 1 year and older who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES). We also describe trends in the total blood Hg of children ages 1-5 (n=3456) and females ages 16-49 during 1999-2006 (n=7245). In the combined 2003-2006 survey periods, the geometric means for non-Hispanic blacks, 0.853microg/L (95% confidence interval [CI], 0.766-0.950microg/L), and non-Hispanic whites, 0.833microg/L (95% CI, 0.752-0.922microg/L), were higher than the geometric mean for Mexican Americans, 0.580microg/L (95% CI, 0.522-0.645microg/L). Also in 2003-2006, regression analysis of log total blood Hg with age, race/ethnicity and gender showed that total blood Hg levels in the population exhibited a quadratic increase with age (p<0.0001), peaking at ages 50-59 in non-Hispanic blacks and whites, at ages 40-49 in Mexican Americans, and then declining at older ages. Over the four survey periods (1999-2006), regression analysis showed that total blood Hg levels increased slightly for non-Hispanic white children and decreased slightly for non-Hispanic black and Mexican American children. Over the same four survey periods, female children had slightly higher total blood Hg levels than males (0.356 vs. 0.313microg/L, p=0.0050) and total blood Hg levels in non-Hispanic black women aged 16-49 years were significantly higher than in non-Hispanic white women (1.081 vs. 0.850microg/L, p<0.0001) and in Mexican American women (1.081 vs. 0.70microg/L, p<0.0001).

Exposure of the U.S. Population to Acrylamide in the National Health and Nutrition Examination Survey 2003-2004

Background The lifelong exposure of the population to acrylamide has raised concerns about the possible health effects of the chemical. Data on the extent of exposure to acrylamide and its primary metabolite, glycidamide, are needed to aid in the assessment of potential health effects. Objectives The aim of this study was to assess human exposure to acrylamide and glycidamide in the general U.S. population through the measurement of hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA). Methods HbAA and HbGA were measured in 7,166 subjects from the National Health and Nutrition Examination Survey. Stratified HbAA and HbGA data were reported by sex, age groups, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white), and smoking status based on serum cotinine levels. Covariate-adjusted geometric means for each demographic group were calculated using multiple regression analysis. Results HbAA and HbGA levels ranged from 3 to 910 and from 4 to 756 pmol/g hemoglobin, respectively, with smokers having the highest levels overall. Tobacco smoke exposure in nonsmokers had a small but significant effect on HbAA and HbGA levels. Adjusted geometric mean levels for children 3–11 years of age were higher than for adults ≥ 60 years of age [mean (95% confidence interval): HbAA, 54.5 (49.1–51.5) and HbGA, 73.9 (71.3–76.6) vs. HbAA, 46.2 (44.3–48.2) and HbGA, 41.8 (38.7–45.2)]. Levels were highest in Mexican Americans [HbAA: 54.8 (51.9–57.8), HbGA: 57.9 (53.7–62.5)], whereas non-Hispanic blacks had the lowest HbGA levels [43.5 (41.1–45.9)]. Conclusions U.S. population levels of acrylamide and glycidamide adducts are described. The high variability among individuals but modest differences between population subgroups suggest that sex, age, and race/ethnicity do not strongly affect acrylamide exposure. Adduct concentration data can be used to estimate relative exposure and to validate intake estimates.

Factors influencing the difference between maternal and cord blood lead

Aims: To determine the factors that affect why some infants receive higher exposures relative to the mother’s body burden than do others. Methods: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at Magee-Womens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead determination. The difference between cord and maternal blood lead concentration (PbB) and a dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium nutrition, and physical activity. Results: Higher blood pressure was associated with relatively greater cord compared with maternal PbB, as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium consumption. Conclusion: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard.

Stable isotope labeling of lead compartments in rats with ultralow lead concentrations

The role of the mammalian skeleton as an endogenous lead source is unclear. This is due in part to difficulties in distinguishing mobilized skeletal lead from other endogenous and exogenous lead sources. Therefore, we have applied ultraclean stable lead isotope techniques to label skeletal and soft tissue lead compartments within the rat with distinguishable lead isotopic signatures. Female Wistar (defined flora) rats were fed 206Pb-enriched drinking water ([Pb] = 110 ng/ml) and sacrificed after durations of 2, 4, 7, and 14 days. Blood, kidney, vertebra, and tibia tissues were analyzed for lead concentrations and stable isotopic compositions. The resulting isotopic ratios in soft (blood and kidney) and skeletal (vertebrae and tibia) tissues differed by approximately 40% after 2 days exposure to the 206Pb tracer. More than 90% of the tracer isotopic signature was contained in the soft tissues after 10 days exposure, while skeletal tissues acquired only approximately 50% of the tracer by the end of the study. Because these animals were maintained under trace metal-clean conditions, they contained lead concentrations in whole blood (0.3-3 ng/g), kidney (11-27 ng/g dry wt), and bone (35-70 ng/g dry wt) tissues that are the lowest known reported for contemporary terrestrial mammals, and they (in bone) are comparable to levels in preindustrial mammals. The elevated concentrations of lead in kidney (fresh weight) relative to levels in blood are consistent with the presence of specific lead-binding sites in the kidney at very low levels of exposure.

Urinary excretion of the N-acetyl cysteine conjugate of cis-1,3-dichloropropene by exposed individuals.

A gas chromatographic-mass spectrometric assay was developed to identify and measure the N-acetyl cysteine conjugate of cis-1,3-dichloropropene. The assay was used to show that individuals exposed to 1,3-dichloropropene vapor during field applications excrete this conjugate in their urine. The recoveries of the conjugate were correlated with the product of airborne concentrations and the duration of exposure (r = 0.83).