Evaluation of reported fatality data associated with workers using respiratory protection in the United States (1990-2012).

OSHA revised the 1971 respiratory protection standard in 1998 to add guidance for selecting and maintaining respirators. Fatality reports from 1990 to 2012 were used to characterize historical trends in fatalities associated with respirators. Industry- and time-specific trends were evaluated to determine the effect of the revision to the standard on respirator-related fatalities; 174 respirator-related deaths were reported. The majority of fatalities were associated with using an airline respirator (n = 34) or the absence of using a respirator in required spaces (n = 38). Overall, 79% of fatalities were associated with asphyxia. Fatalities were associated with improper employee use or lack of employer compliance. Reductions in fatality rates over time appeared to be associated with the revisions to the respirator standard, although other variables may influence rates (eg, controls). Recommendations for employers and employees regarding maintaining safe use of respirators are provided.

The challenge of predicting problematic chemicals using a decision analysis tool: Triclosan as a case study.

Manufacturers lack a reliable means for determining whether a chemical will be targeted for deselection from their supply chain. In this analysis, 3 methods for determining whether a specific chemical (triclosan) would meet the criteria necessary for being targeted for deselection are presented. The methods included a list-based approach, use of a commercially available chemical assessment software tool run in 2 modes, and a public interest evaluation. Our results indicated that triclosan was included on only 6 of the lists reviewed, none of which were particularly influential in chemical selection decisions. The results from the chemical assessment tool evaluations indicated that human and ecological toxicity for triclosan is low and received scores indicating that the chemical would be considered of low concern. However, triclosan's peak public interest tracked several years in advance of increased regulatory scrutiny of this chemical suggesting that public pressure may have been influential in deselection decisions. Key data gaps and toxicity endpoints not yet regulated such as endocrine disruption potential or phototoxicity, but that are important to estimate the trajectory for deselection of a chemical, are discussed. Integr Environ Assess Manag 2017;13:198-207. © 2016 SETAC.

Lung cancer mutation profile of EGFR, ALK, and KRAS: Meta-analysis and comparison of never and ever smokers.

Lung cancer is the leading cause of cancer-related mortality. While the majority of lung cancers are associated with tobacco smoke, approximately 10-15% of U.S. lung cancers occur in never smokers. Evidence suggests that lung cancer in never smokers appears to be a distinct disease caused by driver mutations which are different than the genetic pathways observed with lung cancer in smokers. A meta-analysis of human epidemiologic data was conducted to evaluate the profile of common or therapy-targetable mutations in lung cancers of never and ever smokers. Epidemiologic studies (N=167) representing over 63,000 lung cancer cases were identified and used to calculate summary odds ratios for lung cancer in never and ever smokers containing gene mutations: EGFR, chromosomal rearrangements and fusion of EML4 and ALK, and KRAS. This analysis also considered the effect of histopathology, smoking status, sex, and ethnicity. There were significantly increased odds of presenting the EGFR and ALK-EML4 mutations in 1) adenocarcinomas compared to non-small cell lung cancer and 2) never smokers compared to ever smokers. The prevalence of EGFR mutations was higher in Asian women as compared to women of Caucasian/Mixed ethnicity. As the smoking history increased, there was a decreased odds for exhibiting the EGFR mutation, particularly for cases >30 pack-years. Compared to ever smokers, never smokers had a decreased odds of KRAS mutations among those of Caucasian/Mixed ethnicity (OR=0.22, 95% CI: 0.17-0.29) and those of Asian ethnicity (OR=0.39, 95% CI: 0.30-0.50). Our findings show that key driver mutations and several patient features are highly prevalent in lung cancers of never smokers. These associations may be helpful as patient demographic models are developed to predict successful outcomes of targeted therapeutic interventions NSCLC.

Best-practices approach to determination of blood alcohol concentration (BAC) at specific time points: Combination of ante-mortem alcohol pharmacokinetic modeling and post-mortem alcohol generation and transport considerations.

Alcohol concentrations in biological matrices offer information regarding an individual's intoxication level at a given time. In forensic cases, the alcohol concentration in the blood (BAC) at the time of death is sometimes used interchangeably with the BAC measured post-mortem, without consideration for alcohol concentration changes in the body after death. However, post-mortem factors must be taken into account for accurate forensic determination of BAC prior to death to avoid incorrect conclusions. The main objective of this work was to describe best practices for relating ante-mortem and post-mortem alcohol concentrations, using a combination of modeling, empirical data and other qualitative considerations. The Widmark modeling approach is a best practices method for superimposing multiple alcohol doses ingested at various times with alcohol elimination rate adjustments based on individual body factors. We combined the selected ante-mortem model with a suggestion for an approach used to roughly estimate changes in BAC post-mortem, and then analyzed the available data on post-mortem alcohol production in human bodies and potential markers for alcohol production through decomposition and putrefaction. Hypothetical cases provide best practice approaches as an example for determining alcohol concentration in biological matrices ante-mortem, as well as potential issues encountered with quantitative post-mortem approaches. This study provides information for standardizing BAC determination in forensic toxicology, while minimizing real world case uncertainties.

Analysis of workplace compliance measurements of asbestos by the U.S. Occupational Safety and Health Administration (1984-2011).

The United States Occupational Safety and Health Administration (OSHA) maintains the Chemical Exposure Health Data (CEHD) and the Integrated Management Information System (IMIS) databases, which contain quantitative and qualitative data resulting from compliance inspections conducted from 1984 to 2011. This analysis aimed to evaluate trends in workplace asbestos concentrations over time and across industries by combining the samples from these two databases. From 1984 to 2011, personal air samples ranged from 0.001 to 175 f/cc. Asbestos compliance sampling data associated with the construction, automotive repair, manufacturing, and chemical/petroleum/rubber industries included measurements in excess of 10 f/cc, and were above the permissible exposure limit from 2001 to 2011. The utility of combining the databases was limited by the completeness and accuracy of the data recorded. In this analysis, 40% of the data overlapped between the two databases. Other limitations included sampling bias associated with compliance sampling and errors occurring from user-entered data. A clear decreasing trend in both airborne fiber concentrations and the numbers of asbestos samples collected parallels historically decreasing trends in the consumption of asbestos, and declining mesothelioma incidence rates. Although air sampling data indicated that airborne fiber exposure potential was high (>10 f/cc for short and long-term samples) in some industries (e.g., construction, manufacturing), airborne concentrations have significantly declined over the past 30 years. Recommendations for improving the existing exposure OSHA databases are provided.

Airborne asbestos exposures associated with gasket and packing replacement: a simulation study of flange and valve repair work and an assessment of exposure variables.

A simulation study was conducted to evaluate worker and area exposure to airborne asbestos associated with the replacement of asbestos-containing gaskets and packing materials from flanges and valves and assess the influence of several variables previously not investigated. Additionally, potential of take home exposures from clothing worn during the study was characterized. Our data showed that product type, ventilation type, gasket location, flange or bonnet size, number of flanges involved, surface characteristics, gasket surface adherence, and even activity type did not have a significant effect on worker exposures. Average worker asbestos exposures during flange gasket work (PCME=0.166 f/cc, 12-59 min) were similar to average worker asbestos exposures during valve overhaul work (PCME=0.165 f/cc, 7-76 min). Average 8-h TWA asbestos exposures were estimated to range from 0.010 to 0.062 f/cc. Handling clothes worn during gasket and packing replacement activities demonstrated exposures that were 0.71% (0.0009 f/cc 40-h TWA) of the airborne asbestos concentration experienced during the 5 days of the study. Despite the many variables considered in this study, exposures during gasket and packing replacement occur within a relatively narrow range, are below current and historical occupational exposure limits for asbestos, and are consistent with previously published data.

Evaluation of the California Safer Consumer Products Regulation and the impact on consumers and product manufacturers.

Chemistry enables more than 95% of products in the marketplace. Over the past 20 years, various entities began to generate inventories of chemicals ("chemical watch lists") potentially associated with human or environmental health risks. Some lists included thousands of chemicals, while others listed only a few chemistries with limited properties or toxicological endpoints (e.g., neurotoxicants). Enacted on October 1, 2013, the California Safer Consumer Products Regulation (SCP) utilized data from chemical inventory lists to create one master list. This paper aims to discuss the background and requirements of this regulation. Additionally, we wanted to understand the universe of Candidate Chemicals identified by the Regulation. Data from all 23 chemical lists identified in the SCP Regulation were entered into a database. The most prevalent chemicals among the ∼2900 chemicals are identified, including the most prevalent chemical, lead, appearing on 65% of lists, followed by DEHP (52%), perchloroethylene (48%), and benzene (48%). Our results indicated that the most prevalent Candidate Chemicals were either persistent, bioaccumulative, carcinogenic, or reprotoxic. This regulation will have wide-ranging impact in California and throughout the global supply chain, which is highlighted through selected examples and case studies.

Evaluation of take home (para-occupational) exposure to asbestos and disease: a review of the literature.

The potential for para-occupational (or "take-home") exposure to a number of chemicals has been recognized for over 60 years. We conducted a literature review in order to characterize reported cases of asbestos-related disease among household contacts of workers occupationally exposed to asbestos. Over 200 published articles were evaluated. Nearly 60 articles described cases of asbestos-related disease thought to be caused by para-occupational exposure. Over 65% of these cases were in persons who lived with workers classified as miners, shipyard workers, insulators, or others involved in the manufacturing of asbestos-containing products, with nearly all remaining workers identified as craftsmen. 98% of the available lung samples of the persons with diseases indicated the presence of amphibole asbestos. Eight studies provided airborne asbestos concentrations during (i) handling of clothing contaminated with asbestos during insulation work or simulated use of friction products; (ii) ambient conditions in the homes of asbestos miners; and (iii) wearing previously contaminated clothing. This review indicates that the literature is dominated by case reports, the majority of which involved household contacts of workers in industries characterized, generally, by high exposures to amphiboles or mixed mineral types. The available data do not implicate chrysotile as a significant cause of disease for household contacts. Also, our analysis indicates that there is insufficient information in the published literature that would allow one to relate airborne asbestos concentrations in a workplace to those that would be generated from subsequent handling of contact with clothing that had been contaminated in that environment. Ideally, a simulation study could be conducted in the future to better understand the relationships between the airborne concentrations in the workplace and the fiber characteristics that influence retention on fabric, as well as the concentrations that can be generated by handling the contaminated clothing by the persons in the home.

Biomarkers of manganese intoxication.

Manganese (Mn), upon absorption, is primarily sequestered in tissue and intracellular compartments. For this reason, blood Mn concentration does not always accurately reflect Mn concentration in the targeted tissue, particularly in the brain. The discrepancy between Mn concentrations in tissue or intracellular components means that blood Mn is a poor biomarker of Mn exposure or toxicity under many conditions and that other biomarkers must be established. For group comparisons of active workers, blood Mn has some utility for distinguishing exposed from unexposed subjects, although the large variability in mean values renders it insensitive for discriminating one individual from the rest of the study population. Mn exposure is known to alter iron (Fe) homeostasis. The Mn/Fe ratio (MIR) in plasma or erythrocytes reflects not only steady-state concentrations of Mn or Fe in tested individuals, but also a biological response (altered Fe homeostasis) to Mn exposure. Recent human studies support the potential value for using MIR to distinguish individuals with Mn exposure. Additionally, magnetic resonance imaging (MRI), in combination with noninvasive assessment of γ-aminobutyric acid (GABA) by magnetic resonance spectroscopy (MRS), provides convincing evidence of Mn exposure, even without clinical symptoms of Mn intoxication. For subjects with long-term, low-dose Mn exposure or for those exposed in the past but not the present, neither blood Mn nor MRI provides a confident distinction for Mn exposure or intoxication. While plasma or erythrocyte MIR is more likely a sensitive measure, the cut-off values for MIR among the general population need to be further tested and established. Considering the large accumulation of Mn in bone, developing an X-ray fluorescence spectroscopy or neutron-based spectroscopy method may create yet another novel non-invasive tool for assessing Mn exposure and toxicity.

A cross-sectional analysis of reported corporate environmental sustainability practices.

The concept of sustainability evolved throughout the 1970s and 1980s, but was formally described by the 27 principles of the Rio Declaration on Environment and Development in 1992. Despite the passage of nearly 20years, to date there are no uniform set of federal rules, regulations, or guidelines specifically governing the environmental aspects of sustainability practices or related requirements in the United States. In this benchmark analysis, we have collected information on the sustainability programs of the five largest US companies in each of the 26 industrial sectors [based on the Forbes Global 2000 through 2009 (n=130)]. For each company, we reviewed the most recent corporate sustainability, citizenship, or responsibility report, limiting our scope to environmental components, if available. Ten criteria were identified and analyzed, including leadership, reporting, external review, certification, and individual components of environmental sustainability programs. With respect to the prevalence of sustainability components between various business sectors, we found that the Drugs and Biotechnology (87%), Household and Personal Products (87%) and Oil and Gas Operations (87%) industries had the most comprehensive environmental sustainability programs. Using the nine components of environmental sustainability as a benchmark, we identified four key components as the characteristics of the most comprehensive environmental sustainability programs. These were (1) empowering leadership with a commitment to sustainability (80%), (2) standardized reporting (87%), (3) third-party evaluation of the sustainability programs (73%), and (4) obtaining ISO 14001 certification (73%). We found that many firms shaped their own definition of sustainability and developed their associated sustainability programs based on their sector, stakeholder interests, products or services, and business model. We noted an emerging area that we have called product sustainability - one in which toxicologists and environmental scientists can play a vital role helping to ensure that a manufactured item will indeed be considered acceptable for distribution now, as well as in the coming years. Numerous examples or case studies are presented.

Manganese exposure among smelting workers: relationship between blood manganese-iron ratio and early onset neurobehavioral alterations.

A biomarker for detection of early onset neurobehavioral alterations in manganism remains unknown. The purpose of this study was to use a neurobehavioral test battery to identify subtle changes in Mn-induced motor and memory dysfunction and to relate the quantifiable neurological dysfunction to an established Mn-exposure index such as blood manganese-iron ratio (MIR). A total of 323 subjects were recruited to control (n=106), low-exposure (122), and high-exposure (95) groups. The test battery consisted of standard testing procedures including the nine-hole and groove-type steadiness tester, Benton visual retention test, and Purdue pegboard coordination test. No significant health problems or clinically diagnosed neurological dysfunctions were observed. Benton test did not reveal any abnormal memory deficits among Mn-exposed smelters, nor did the groove and nine-hole tests detect any abnormality in dynamic and static steadiness in tested subjects. Purdue pegboard test showed a remarkable age-related decline in fine movement coordination among all study participants regardless of the Mn-exposure condition. Mn exposure significantly exacerbated this age-related deterioration. Statistical modeling revealed that the plasma and erythrocyte MIR (i.e., pMIR and eMIR, respectively) were associated with Purdue pegboard scores. Among all subjects whose MIR were above the cut-off value (COV), pMIR was significantly correlated with pegboard scores (r=-0.261, p=0.002), whereas for those subjects over the age of 40, the eMIR, but not pMIR, was associated with declined pegboard performance (r=-0.219, p=0.069). When both factors were taken into account (i.e., age>40 and MIR>the COV), only pMIR was inversely associated with pegboard scores. Combining their usefulness in Mn-exposure assessment, we recommend that the blood Mn-Fe ratio may serve as a reasonable biomarker not only for assessment of Mn exposure but also for health risk assessment.

Manganese exposure among smelting workers: blood manganese-iron ratio as a novel tool for manganese exposure assessment.

Unexposed control subjects (n = 106), power distributing and office workers (n = 122), and manganese (Mn)-exposed ferroalloy smelter workers (n = 95) were recruited to the control, low and high groups, respectively. Mn concentrations in saliva, plasma, erythrocytes, urine and hair were significantly higher in both exposure groups than in the controls. The Fe concentration in plasma and erythrocytes, however, was significantly lower in Mn-exposed workers than in controls. The airborne Mn levels were significantly associated with Mn/Fe ratio (MIR) of erythrocytes (eMIR) (r = 0.77, p < 0.01) and plasma (pMIR) (r = 0.70, p < 0.01). The results suggest that the MIR may serve as a useful biomarker to distinguish Mn-exposed workers from the unexposed, control population.

Chelation therapy of manganese intoxication with para-aminosalicylic acid (PAS) in Sprague-Dawley rats.

Para-aminosalicylic acid (PAS), an FDA-approved anti-tuberculosis drug, has been used successfully in the treatment of severe manganese (Mn)-induced Parkinsonism in humans [Jiang Y-M, Mo X-A, Du FQ, Fu X, Zhu X-Y, Gao H-Y, et al. Effective treatment of manganese-induced occupational Parkinsonism with p-aminosalicylic acid: a case of 17-year follow-up study. J Occup Environ Med 2006;48:644-9]. This study was conducted to explore the capability of PAS in reducing Mn concentrations in body fluids and tissues of Mn-exposed animals. Sprague-Dawley rats received daily intraperitoneally (i.p.) injections of 6mg Mn/kg, 5 days/week for 4 weeks, followed by a daily subcutaneously (s.c.) dose of PAS (100 and 200mg/kg as the PAS-L and PAS-H group, respectively) for another 2, 3 or 6 weeks. Mn exposure significantly increased the concentrations of Mn in plasma, red blood cells (RBC), cerebrospinal fluid (CSF), brain and soft tissues. Following PAS-H treatment for 3 weeks, Mn levels in liver, heart, spleen and pancreas were significantly reduced by 25-33%, while 3 weeks of PAS-L treatment did not show any effect. Further therapy with PAS-H for 6 weeks reduced Mn levels in striatum, thalamus, choroid plexus, hippocampus and frontal cortex by 16-29% (p<0.05). Mn exposure greatly increased iron (Fe) and copper (Cu) concentrations in CSF, brain and liver. Treatment with PAS-H restored Fe and Cu levels comparable with control. These data suggest that PAS likely acts as a chelating agent to mobilize and remove tissue Mn. A high-dose and prolonged PAS treatment appears necessary for its therapeutic effectiveness.