Evaluation of ATSDR's MRL and EPA's RfCs/RfDs: Similarities, Differences, and Rationales.

Objectives: The Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA) derive minimal risk levels (MRLs) and reference concentrations and doses (RfCs and RfDs), respectively, for environmental contaminants to help identify potential health risks to exposed populations. MRLs, RfDs, and RfCs involve similar derivation methods, but the values sometimes differ for the same chemical. The objectives of this manuscript are to quantitatively assess similarities and differences between MRLs, RfCs, and RfDs, qualitatively describe how a number of factors can influence the development of the health guidance values (HGVs) and identify ongoing collaborations and opportunities for increased coordination of efforts. Materials and Methods: We collected MRLs and RfCs/RfDs, assessment date, and description of the derivation process from ATSDR's toxicological profiles and EPA's Integrated Risk Information System (IRIS) and Office of Pesticide Program (OPP) and identified reasons for differences between MRLs and RfCs/RfDs. Results: The most frequent types of differences in values that we found in our analysis included use of different methodologies, use of different studies, and/or completion of a more recent chemical evaluation. These can stem from differences in scientific judgement. Conclusion: To avoid confusion when disparate HGVs occur between government agencies, a keen understanding of these differences can be helpful for appropriate risk characterization and communication when applying HGVs.

Description of exposure profiles for seven environmental chemicals in a US population using recursive partition mixture modeling (RPMM).

Biomonitoring studies have shown that humans are exposed to numerous environmental chemicals. Previous work provides limited insights into the dynamic relationship between different chemicals within a population. The objective of this study is to develop an analytical method identifying exposure profiles of seven common environmental chemicals and determine how exposure profiles differ by sociodemographic groups and National Health and Nutrition Examination Survey (NHANES) 2003-2012 cycle year. We used recursive partition mixture modeling (RPMM) to define classes of the population with similar exposure profiles of lead, cadmium, 2,4-dichlorophenol, 2,5-dichlorophenol, bisphenol A (BPA), triclosan, and benzophenone-3 in individuals aged ≥6 years. Additionally, quasibinomial logistic regression was used to examine the association between each class and selected demographic characteristics. Eight exposure profiles were identified. Individuals who clustered together and had the highest chemical exposures were more likely to be older, to be Non-Hispanic Black (NHB) or Other Hispanic (OH), more likely to live below the poverty line, more likely to be male, and more likely to have participated in the earlier NHANES cycle (2003-2004). The developed method described the dynamic relationship between chemicals and shows that this relationship is different for subpopulations based on their sociodemographic characteristics.

Age and sex differences in hearing loss association with depressive symptoms: analyses of NHANES 2011-2012.

BACKGROUND: Depression is a common and significant health problem. Hearing loss is the third most common chronic physical condition in the USA and might be a factor in depression. To determine whether hearing loss is associated with depressive symptoms in US adults ages 20-69 years. METHODS: National Health and Nutrition Examination Survey (NHANES) data (2011-2012) were used to assess the potential relationship between hearing loss and depression, in adults (20-69 years) who answered the Patient Health Questionnaire (PHQ-9) depression screening module, with pure tone audiometry measurements, and complete information on the co-variates data (n = 3316). The degree of speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL) were defined as slight/mild hearing loss ⩾26-40 dB; moderate/worse hearing loss ⩾41 dB by pure tone audiometry examination. RESULTS: Moderate/worse HFHL was statistically significantly associated with depressive symptoms (OR 1.54, 95% CL 1.04-2.27) when the analyses were conducted among all participants. Further stratification by gender and age groups found that moderate/worse HFHL (OR 3.85, 95% CL 1.39-10.65) and moderate/worse SFHL (OR 5.75, 95% CL 1.46-22.71) were associated with depressive symptoms in women ages 52-69 years. CONCLUSIONS: Moderate/worse speech frequency and HFHL are associated with depression in women ages 52-69 years, independent of other risk factors. Hearing screenings are likely to reduce delays in diagnosis and provide early opportunities for noise prevention counseling and access to hearing aids. Health professionals should be aware of depressive signs and symptoms in patients with hearing loss.

A cross sectional study of urinary phthalates, phenols and perchlorate on thyroid hormones in US adults using structural equation models (NHANES 2007-2008).

BACKGROUND: Biomonitoring data shows that people are exposed to phthalates, phenols and perchlorates. Many of these compounds are endocrine disrupting compounds that affect thyroid hormone levels. Yet the effect of these compounds on thyroid hormone levels are often evaluated individually rather than as a mixture. Our objective was to examine the association between 11 urinary endocrine disrupting compounds and thyroid hormones using structural equation models. METHODS: Using data from the National Health and Nutrition and Examination Survey 2007-2008, we fit a latent variable utilizing urinary measurements of 9 compounds in females (perchlorate, bisphenol A, benzophenone-3, mono-2ethyl5carboxypentyl phthalate, mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono(2ethyl5hydroxyhexyl) phthalate, mono-benzyl phthalate, and mono-isobutyl phthalate) and 8 compounds in males (without benzophenone-3). The association of the latent variable with serum thyroid hormones (Total T3, Total T4, and Thyroid Stimulating Hormones) was assessed in females (N = 710) and males (N = 850) over the age of 12 controlling for age, race, and urinary creatinine. RESULTS: In males, urinary endocrine disrupting compound levels were negatively associated with thyroxine (ß: -0.19, 95% Confidence Interval (95% CI): -0.31, -0.05). In females, urinary endocrine disrupting compound levels were positively associated with triiodothyronine serum concentrations (ß: 0.09, 95% CI: -0.03, 0.21) however this association was not statistically significant. CONCLUSIONS: This cross-sectional analysis provides additional evidence that environmental exposure to phthalates and phenols is associated with endocrine-related processes. Furthermore, these results suggested sex-specific differences in exposure to endocrine disrupting mixtures, and the exposure-response between endocrine disrupting mixtures and thyroid hormone levels. Specifically, higher exposure to a mixture of endocrine disrupting compounds was associated with lower levels of total T4 in males but not in females. While a structural methodological framework was used to assess these complex relationships, the cross sectional nature of this analysis limits causal inference and further research is needed to determine the clinical significance of these findings.

A path analysis of multiple neurotoxic chemicals and cognitive functioning in older US adults (NHANES 1999-2002).

BACKGROUND: Polychlorinated biphenyls (PCBs) and metals (lead and cadmium) are neurotoxic and affect neurobehavioral performance. Yet little is known about the association between exposure to multiple neurotoxic compounds and cognitive functioning in older adults. METHODS: Using data from two consecutive cycles of the National Health and Nutrition and Examination Survey (1999-2002), path analysis was used to simultaneously evaluate the association between whole blood concentrations of 14 neurotoxic compounds and cognitive functioning measured by the Digit Symbol Coding Test of the Weschler Adult Intelligence Scale, 3rd Edition in participants 60-84 years of age (N = 498). Effect modification was assessed for age (above/below the mean) and sex. RESULTS: The final path model fit 5 compounds (i.e. PCB 74, PCB 118, PCB 146, PCB 153, and lead). After controlling for co-exposures and confounders, PCB 146 (ß = -0.16, 95% CI: -0.29, -0.02, p = 0.02) and lead (ß = -0.10, 95% CI: -0.20, -0.006, p = 0.04) were negatively associated with DSC scores in 60-84 year olds. Whereas, PCB 153 was positively associated with DSC scores (ß =0.20, 95% CI: 0.05, 0.35; p = 0.01). CONCLUSIONS: This cross-sectional analysis which controlled for collinear exposure to several neurotoxic compounds demonstrated an association between non-dioxin like polychlorinated biphenyl exposure, specifically PCB 146, and lower cognitive functioning, in older adults. Lead exposure was also weakly associated with lower cognitive functioning. Additional studies are needed to determine the causality of the observed associations.

Cross-Sectional Study of Polybrominated Flame Retardants and Self-Reported Attention Deficit Hyperactivity Disorder in US Youth Aged 12-15 (NHANES 2003-2004).

Background. Animal toxicity tests and epidemiological studies suggest that exposure to PBDEs can alter attention behavior, yet few studies have examined their association with diagnosis of attention deficit hyperactivity disorder (ADHD) in adolescents. Methods. Logistic regression was used to examine the cross-sectional association between ADHD and lipid and non-lipid adjusted blood serum concentrations of 2',4-tribromodiphenyl ether (BDE-28), 2,2',4,4'-tetrabromodiphenylether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), 2,2',4,4',5,5'-pentabromodiphenyl ether (BDE-100), 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153), serum PBDEs, above/below the 75th percentile of serum PBDEs, and tertiles of serum PBDE in 12-15-year-olds (N = 292) using the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Results. The ADHD weighted prevalence was 13.57%. The weighted adjusted odds ratios (AOR) and 95% confidence interval (CI) between ADHD diagnosis and lipid adjusted BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, serum total PBDE, serum PBDE concentrations above the 75th percentile, and serum PBDE concentrations in the second or third tertile were 1.16 (95% CI: 0.51, 2.67), 1.36 (95% CI: 0.72, 2.56), 1.51 (95% CI: 0.70, 3.25), 1.53 (95% CI: 0.73, 3.23), 1.43 (95% CI: 0.57, 3.56), 1.41 (0.71, 2.83), 0.59 (0.10, 3.56), 6.16 (1.19, 31.90), and 0.99 (0.23, 4.29). Conclusions. We observed no association between serum PBDE concentrations and ADHD in US youths.

Neurodevelopmental low-dose bisphenol A exposure leads to early life-stage hyperactivity and learning deficits in adult zebrafish.

Developmental bisphenol A (BPA) exposure has been implicated in adverse behavior and learning deficits. The mode of action underlying these effects is unclear. The objectives of this study were to identify whether low-dose, developmental BPA exposure affects larval zebrafish locomotor behavior and whether learning deficits occur in adults exposed during development. Two control compounds, 17ß-estradiol (an estrogen receptor ligand) and GSK4716 (a synthetic estrogen-related receptor gamma ligand), were included. Larval toxicity assays were used to determine appropriate BPA, 17ß-estradiol, and GSK4716 concentrations for behavior testing. BPA tissue uptake was analyzed using HPLC and lower doses were extrapolated using a linear regression analysis. Larval behavior tests were conducted using a ViewPoint Zebrabox. Adult learning tests were conducted using a custom-built T-maze. BPA exposure to <30µM was non-teratogenic. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1µM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1µM 17ß-estradiol or GSK4716 also led to larval hyperactivity. This study demonstrates the efficacy of using the zebrafish model for studying the neurobehavioral effects of low-dose developmental BPA exposure.

Analysis of fiber blends using horizontal attenuated total reflection Fourier transform infrared and discriminant analysis.

We have investigated the utility of a horizontal attenuated total reflection Fourier transform infrared spectrometer (HATR/FT-IR) for the analysis of fiber and textile blends. The identification of a blended textile can be accomplished by subtracting a reference spectrum of the textile's most abundant component, leading to a difference spectrum that infers the identity of the second constituent of the blended textile. Mathematical post-processing of the spectra employing discriminant analysis provided a useful statistical tool to confirm the fiber blend components.