A case is presented of the attempted suicide of a 58-year-old man using castor beans. The patient came to the emergency room complaining of nausea, vomiting and diarrhea for nine hours following the ingestion of six castor beans. Urine samples were taken throughout the hospital stay and submitted to the Centers for Disease Control and Prevention for analysis of ricinine, a castor bean component. The samples were found to be positive for ricinine, with a maximum concentration of 674 microg/g-creatinine excreted approximately 23 h post-exposure. Subsequent samples demonstrated lower ricinine concentrations, with the final sample taken at 62 h post-exposure at a concentration of 135 microg/g-creatinine of ricinine. The estimated urinary excretion half-life was approximately 15 h and the recovery of ricinine in the urine over the three days was estimated to be less than 10%. The patient fully recovered with supportive care and was discharged from the hospital six days after admission.

BACKGROUND: Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects. OBJECTIVE: The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency. DESIGN: Data from NHANES, a nationally representative cross-sectional survey, were examined for adults aged >19 y (mean +/- SD age: 45 +/- 1 y) from 1999 to 2004 (n = 12,612). RESULTS: Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of >148 pmol/L for vitamin B-12 and of ≤210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency. CONCLUSIONS: These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal.

Tobacco smoke is a major source of adult exposure to cadmium (Cd). Urine Cd levels (CdU) above 1.0, 0.7, and 0.5mugCd/g creatinine have been associated with increased rates of microproteinuria and reduction in glomerular filtration rate. The two study objectives were to determine the prevalence and relative risk (RR) by smoking status for CdU above 1.0, 0.7, and 0.5mugCd/g creatinine in U.S. adults; and to describe geometric mean CdU by smoking status, age, and sex. NHANES 1999-2006 data for adults without chronic kidney disease were used to compute prevalence rates above the three CdU in current and former cigarette smokers, and non-smokers. RRs for smokers adjusted for age and sex were computed by logistic regression. Analysis of covariance was used to calculate geometric means of CdU adjusted for age, sex, smoking status, log urine creatinine, and interaction terms: age-smoking status and sex-smoking status. At selected ages, adjusted RR for exceeding each risk-associated CdU was highest for current smokers (3-13 times), followed by former smokers (2-3 times), compared to non-smokers. Adjusted RR for smokers increased with age and was higher in females than males. Adjusted geometric means of CdUs increased with age, were higher in females than in males regardless of smoking status, and were higher in current smokers than former smokers, who had higher levels than non-smokers at any age. Cigarette smoking greatly increases RR of exceeding renal risk-associated CdU. Former smokers retain significant risk of exceeding these levels compared to non-smokers. CdU increased with age, particularly in current smokers.

The Agency for Toxic Substances and Disease Registry (ATSDR) is mandated by the US Congress to identify significant human exposure levels, develop methods to determine such exposures, and design strategies to mitigate them. Physiologically based pharmacokinetic (PBPK) models are increasingly being used to evaluate toxicity of environmental pollutants through multiple exposure pathways. As part of its translational research project, ATSDR is developing a human 'PBPK model tool kit' that consists of a series of published models re-coded in a common simulation language. The tool kit currently consists of models, at various stages of development, for priority environmental contaminants including solvents and persistent organic pollutants. Presented here are results of translational activities of re-coding models for cadmium, mercury, and arsenic. As part of this work, following re-coding each new model was evaluated for fidelity followed by sensitivity analysis. Good agreement was generally obtained for all three models when predictions of original and re-coded model simulations were compared. Also presented is an application of the cadmium toxicokinetic model to interpret biomonitoring data from the National Health and Nutrition Examination Survey (NHANES). The PBPK tool kit will enable ATSDR scientists to perform simulations of exposures from contaminated environmental media at sites of concern and to better interpret site-specific biomonitoring data.

This study's goal was to determine cadmium (Cd), lead (Pb), total mercury (THg), and inorganic mercury (IHg) levels in human cadavers to compare measured levels with established reference ranges for living persons and to determine whether blood levels varied with time from death to sample collection or by body collection site. Subjects (n = 66) recruited from the Fulton County Medical Examiner's Office in Atlanta, GA, were 20 years of age or older, had no penetrating trauma, no obvious source of environmental contamination of the vasculature, and had whole blood accessible from the femoral (F) site, the cardiac (C) site, or both. Geometric mean results were as follows: 2.59 microg/L F-Cd; 11.81 microg/L C-Cd; 1.03 microg/L F-THg; 2.01 microg/L C-THg; 0.29 microg/L F-IHg; 0.49 microg/L C-IHg; 1.78 microg/dL F-Pb; and 1.87 microg/dL C-Pb. Both F- and C-Cd levels as well as C-THg levels were significantly higher than reference values among living persons (C- and F-Cd, p < 0.0001 and C-THg, p = 0.0001, respectively). Based on regression modeling, as the postmortem interval increased, blood Cd levels increased (p < 0.006). Postmortem blood Cd concentrations were elevated compared to population values and varied with respect to sampling location and postmortem interval.

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 311 years of age were higher than for adults ≥ 60 years of age [mean (95% confidence interval): HbAA, 54.5 (49.151.5) and HbGA, 73.9 (71.376.6) vs. HbAA, 46.2 (44.348.2) and HbGA, 41.8 (38.745.2)]. Levels were highest in Mexican Americans [HbAA: 54.8 (51.957.8), HbGA: 57.9 (53.762.5)], whereas non-Hispanic blacks had the lowest HbGA levels [43.5 (41.145.9)]. 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. EDITOR'S SUMMARY: Human exposure to acrylamide, a neurotoxin and suspected human carcinogen, occurs via dietary sources, tobacco smoke, and occupational production or use. Carcinogenic effects are attributed to DNA adducts formed with the phase I metabolite glycidamide, and body burdens and risks may be partly determined by factors that influence acrylamide metabolism, including genetic variants and factors that induce metabolism gene expression (e.g., medications and alcohol). Vesper et al. (p. 278) measured hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) in blood samples from 7,166 participants in the National Health and Nutrition Examination Survey, and estimated HbGA:HbAA ratios to assess variation in metabolic conversion. The authors report that smokers had the highest adjusted geometric mean levels of HbAA and HbGA and that adduct levels in nonsmokers were associated with tobacco smoke exposure (based on serum cotinine levels). In addition, adduct levels and HbGA:HbAA ratios were higher in children 311 years of age than in adults ≥ 60 years of age, and in Mexican Americans compared with other participants. The authors note that differences among population subgroups were modest relative to differences among individuals within subgroups, and suggest that factors other than sex, age, and race/ethnicity may be primarily responsible for variation in acrylamide exposure and metabolism.

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).