The Agency for Toxic Substances and Disease Registry (ATSDR) develops interaction profiles using binary weight of evidence (BINWOE) methodology to determine interaction directions of common environmental mixtures. We collected direction of interactions, BINWOE score determination, and BINWOE score confidence rating from 14 interaction profiles along with toxicodynamic and toxicokinetic influences on interaction direction. By doing so, we quantified the 1) direction of interaction and indeterminate evaluations; 2) characterized confidence in the BINWOE determinations; and 3) quantified toxicokinetic/toxicodynamic, and other influences on projected BINWOE interaction directions. Thirty-nine percent (130/336) of the attempts to make a BINWOE were indeterminate due to no interaction data or inadequate or conflicting evidence. Out of remaining BINWOEs ∼25% were additive, ∼9% were greater-than-additive, and 27% were less-than-additive interactions. Fifty-five percent of BINWOEs were explained by toxicokinetic interactions, 12% and 5% were explained by toxicodynamic and other explanations, respectively. High quality mixture toxicology in vivo studies along with mixture in vitro and in silico studies will lead to greater confidence in interaction directions and influences. Limitations for interpretation of the data were also included.

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.

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.