John Snawder

Systemic Exposure to PAHs and Benzene in Firefighters Suppressing Controlled Structure Fires

Turnout gear provides protection against dermal exposure to contaminants during firefighting; however, the level of protection is unknown. We explored the dermal contribution to the systemic dose of polycyclic aromatic hydrocarbons (PAHs) and other aromatic hydrocarbons in firefighters during suppression and overhaul of controlled structure burns. The study was organized into two rounds, three controlled burns per round, and five firefighters per burn. The firefighters wore new or laundered turnout gear tested before each burn to ensure lack of PAH contamination. To ensure that any increase in systemic PAH levels after the burn was the result of dermal rather than inhalation exposure, the firefighters did not remove their self-contained breathing apparatus until overhaul was completed and they were >30 m upwind from the burn structure. Specimens were collected before and at intervals after the burn for biomarker analysis. Urine was analyzed for phenanthrene equivalents using enzyme-linked immunosorbent assay and a benzene metabolite (s-phenylmercapturic acid) using liquid chromatography/tandem mass spectrometry; both were adjusted by creatinine. Exhaled breath collected on thermal desorption tubes was analyzed for PAHs and other aromatic hydrocarbons using gas chromatography/mass spectrometry. We collected personal air samples during the burn and skin wipe samples (corn oil medium) on several body sites before and after the burn. The air and wipe samples were analyzed for PAHs using a liquid chromatography with photodiode array detection. We explored possible changes in external exposures or biomarkers over time and the relationships between these variables using non-parametric sign tests and Spearman tests, respectively. We found significantly elevated (P < 0.05) post-exposure breath concentrations of benzene compared with pre-exposure concentrations for both rounds. We also found significantly elevated post-exposure levels of PAHs on the neck compared with pre-exposure levels for round 1. We found statistically significant positive correlations between external exposures (i.e. personal air concentrations of PAHs) and biomarkers (i.e. change in urinary PAH metabolite levels in round 1 and change in breath concentrations of benzene in round 2). The results suggest that firefighters wearing full protective ensembles absorbed combustion products into their bodies. The PAHs most likely entered firefighters’ bodies through their skin, with the neck being the primary site of exposure and absorption due to the lower level of dermal protection afforded by hoods. Aromatic hydrocarbons could have been absorbed dermally during firefighting or inhaled during the doffing of gear that was off-gassing contaminants.

The Role of Toxicological Science in Meeting the Challenges and Opportunities of Hydraulic Fracturing

We briefly describe how toxicology can inform the discussion and debate of the merits of hydraulic fracturing by providing information on the potential toxicity of the chemical and physical agents associated with this process, individually and in combination. We consider upstream activities related to bringing chemical and physical agents to the site, on-site activities including drilling of wells and containment of agents injected into or produced from the well, and downstream activities including the flow/removal of hydrocarbon products and of produced water from the site. A broad variety of chemical and physical agents are involved. As the industry expands this has raised concern about the potential for toxicological effects on ecosystems, workers, and the general public. Response to these concerns requires a concerted and collaborative toxicological assessment. This assessment should take into account the different geology in areas newly subjected to hydraulic fracturing as well as evolving industrial practices that can alter the chemical and physical agents of toxicological interest. The potential for ecosystem or human exposure to mixtures of these agents presents a particular toxicological and public health challenge. These data are essential for developing a reliable assessment of the potential risks to the environment and to human health of the rapidly increasing use of hydraulic fracturing and deep underground horizontal drilling techniques for tightly bound shale gas and other fossil fuels. Input from toxicologists will be most effective when employed early in the process, before there are unwanted consequences to the environment and human health, or economic losses due to the need to abandon or rework costly initiatives.

Evaluation of Some Potential Chemical Exposure Risks During Flowback Operations in Unconventional Oil and Gas Extraction: Preliminary Results

Approximately 562,000 workers were employed in the U.S. oil and gas extraction industry in 2012; nearly half of those workers were employed by well servicing companies, which include companies that conduct hydraulic fracturing and flowback operations.(1) To understand possible risks for chemical exposures in modern oil and gas extraction operations, the National Institute for Occupational Safety and Health (NIOSH) initiated the Field Effort to Assess Chemical Exposures in Oil and Gas Workers.(2) Initial research identified exposure risks for respirable crystalline silica during hydraulic fracturing as an occupational health hazard.(3–5) This report describes industrial hygiene sampling during flowback operations at six unconventional oil and gas extraction sites in Colorado and Wyoming during spring and summer 2013. The results are considered preliminary; additional exposure assessments are needed to better understand the range of possible exposures, risk factors, and controls during flowback operations.

Depression of constitutive murine cytochromes P450 by staphylococcal enterotoxin B

Most in vivo studies demonstrating decreased activities of hepatic cytochromes P450 with inflammation have used Gram-negative bacterial lipopolysaccharide (LPS) as the inflammatory stimulant. But products of Gram-positive bacteria, such as staphylococcal enterotoxin B (SEB), also stimulate inflammatory mediators, albeit with a different pattern than LPS. Therefore, effects of SEB on the regulation of murine constitutive P450s were determined in this study and compared with those of LPS. LPS-responsive C3H/HeN and LPS-unresponsive C3H/HeJ mice were injected with either LPS (0.5 mg/kg) or SEB (0.66 to 6.6 mg/kg), and hepatic cytochromes P450 and serum tumor necrosis factor-alpha, interleukin-6, nitrate/nitrite, and serum amyloid A concentrations were determined up to 24 hr. HeJ mice were generally less responsive than HeN mice to both stimuli, with lower cytokine, nitrate/nitrite, and serum amyloid A responses. However, in both mouse strains SEB caused more prolonged cytokine, higher nitrate/nitrite, and lower serum amyloid A concentrations than LPS. Despite these differences, in HeN mice, after both SEB and LPS administration, total P450 concentrations were equally depressed by 40%. Both SEB and LPS depressed CYP1A1 and 1A2 microsomal protein concentrations by 45 and 30%, respectively; CYP2E1 by 64%; and CYP3A by 70%. There was comparable inhibition of enzymatic activities. In HeJ mice, SEB was only slightly more effective in depressing P450s than LPS, as might be expected. These data showed that the Gram-positive bacterial inflammatory stimulant SEB caused effects on murine hepatic cytochromes P450 similar to those of LPS, even though the pattern of inflammatory mediators induced after SEB exposure was different.

Measurement of multiple drugs in urine, water, and on surfaces using fluorescence covalent microbead immunosorbent assay

There are a range of applications that require the measurement of multiple drugs such as urine analysis, drug determination in water, and screening for drug contamination on surfaces. Some of the procedures used such as enzyme-linked immunosorbent assay (ELISA) are simple but can only determine one drug at a time, and others such as GC-MS or LC-MS are complex, time-consuming, and expensive. In this study, fluorescence covalent microbead immunosorbent assay (FCMIA) was investigated as a simple method for the measurement of multiple drugs simultaneously in three matrices: diluted urine, water, and on surfaces. Five different drugs of abuse or their metabolites (methamphetamine, caffeine, benzoylecgonine (a metabolite of cocaine), tetrahydrocannabinol (THC), the active ingredient in marijuana, and oxycodone) were studied over the range 0–15 ng/ml. There was no measureable cross-reactivity among the drugs at the concentrations studied. Urine dilutions from 1/50 to 1/2.5 were studied and dilutions less than 1/20 had a significant effect on the methamphetamine assay but limited effects on the benzoylecgonine and oxycodone assays and almost no effect on the THC assay. For assays performed in 1/20 urine dilution, water, and diluted surface sampling buffer, least detectable doses (LDD) were 1 ng/ml or less for the drugs. Surfaces spiked with drugs were sampled with swabs wetted with surface sampling buffer and recoveries were linear over the range 0–100 ng/100 cm2 surface loading for all drugs. FCMIA has potential to be used for the measurement of multiple drugs in the matrices studied.

Micronucleus Frequencies in Lymphocytes and Reticulocytes in a Pesticide-Exposed Population in Portugal

A wide range of chemical products known to be acutely toxic is currently used in the agricultural sector, including numerous pesticides with different compositions. Nevertheless, the effects in human health as result of chronic exposure to low levels are not yet completely understood. The methodology for determination of micronuclei (MN) in lymphocytes (CBMN) is well established, and accumulating data demonstrated a correlation to enhanced risk of cancer development. However, analysis of MN in reticulocytes (MN-RET) in humans is a recent tool on human biomonitoring. The aim of this study was to examine the influence of pesticide exposure on MN-RET and CBMN frequencies. In total, 177 individuals were studied (93 controls and 84 exposed). All individuals included in the exposed group were exposed regularly to various chemicals. Both MN-RET and CBMN were significantly higher in the exposed subjects compared to controls. The CBMN frequencies were quantitatively higher in females than males, especially within the exposed group. Smoking habits exerted no marked influence on the frequency of the biomarkers studied. A significant and positive correlation was found between both indicators. Within the exposed group, data showed that there was a significant correlation between MN-RET and recent exposure (exposure in the previous 10 d) that is not found when considering CBMN. It is conceivable that due to the short life span of reticulocytes, MN-RET were found to be more reliable to characterize recent genetic damage as opposed to CBMN.

Recommendations for Biomonitoring of Emergency Responders: Focus on Occupational Health Investigations and Occupational Health Research

The disaster environment frequently presents rapidly evolving and unpredictable hazardous exposures to emergency responders. Improved estimates of exposure and effect from biomonitoring can be used to assess exposure-response relationships, potential health consequences, and effectiveness of control measures. Disaster settings, however, pose significant challenges for biomonitoring. A decision process for determining when to conduct biomonitoring during and following disasters was developed. Separate but overlapping decision processes were developed for biomonitoring performed as part of occupational health investigations that directly benefit emergency responders in the short term and for biomonitoring intended to support research studies. Two categories of factors critical to the decision process for biomonitoring were identified: Is biomonitoring appropriate for the intended purpose and is biomonitoring feasible under the circumstances of the emergency response? Factors within these categories include information needs, relevance, interpretability, ethics, methodology, and logistics. Biomonitoring of emergency responders can be a valuable tool for exposure and risk assessment. Information needs, relevance, and interpretability will largely determine if biomonitoring is appropriate; logistical factors will largely determine if biomonitoring is feasible. The decision process should be formalized and may benefit from advance planning.

A Pilot Study of Workplace Dermal Exposures to Cypermethrin at a Chemical Manufacturing Plant

Exposure during the manufacture of pesticides is of particular concern due to their toxicity and because little is known about worker exposure, since most studies have focused on end-use application within agriculture or buildings. Even though dermal exposure can be expected to dominate for pesticides, little is known about workplace dermal exposures or even appropriate methods for their assessment. The current study begins to address this gap by evaluating alternative methods for assessing dermal exposure at a chemical manufacturing plant. For this pilot study, eight workers were recruited from a U.S. plant that produced the pesticide cypermethrin. Exposure was evaluated using three approaches: (1) survey assessment (questionnaire), (2) biological monitoring, and (3) workplace environmental sampling including ancillary measurements of glove contamination (interior and exterior). In each case, cypermethrin was quantified by enzyme-linked immunosorbent assay (ELISA). Environmental measurements identified two potential pathways of cypermethrin exposure: glove and surface contamination. Workplace exposure was also indicated by urine levels (specific gravity adjusted) of the parent compound, which ranged from 35 to 253 μg/L (median of 121 μg/L) with no clear trend in levels from pre- to post-shift. An exploratory analysis intended to guide future studies revealed a positive predictive association (Spearman correlation, p ≤ 0.10) between post-shift urine concentrations and a subset of survey questions evaluating worker knowledge, attitudes, and perceptions (KAP) of workplace dermal hazards, i.e., personal protective equipment self-efficacy, and inverse associations with behavior belief and information belief scales. These findings are valuable in demonstrating a variety of dermal exposure methods (i.e., behavioral attributes, external contamination, and biomarker) showing feasibility and providing measurement ranges and preliminary associations to support future and more complete assessments. Although these pilot data are useful for supporting design and sample size considerations for larger exposure and health studies, there is a need for validation studies of the ELISA assay for quantification of cypermethrin and its metabolites in urine.

Measurement of area and personal breathing zone concentrations of diesel particulate matter (DPM) during oil and gas extraction operations, including hydraulic fracturing

ABSTRACT Diesel engines serve many purposes in modern oil and gas extraction activities. Diesel particulate matter (DPM) emitted from diesel engines is a complex aerosol that may cause adverse health effects depending on exposure dose and duration. This study reports on personal breathing zone (PBZ) and area measurements for DPM (expressed as elemental carbon) during oil and gas extraction operations including drilling, completions (which includes hydraulic fracturing), and servicing work. Researchers at the National Institute for Occupational Safety and Health (NIOSH) collected 104 full-shift air samples (49 PBZ and 55 area) in Colorado, North Dakota, Texas, and New Mexico during a four-year period from 2008–2012. The arithmetic mean (AM) of the full shift TWA PBZ samples was 10 µg/m3; measurements ranged from 0.1–52 µg/m3. The geometric mean (GM) for the PBZ samples was 7 µg/m3. The AM of the TWA area measurements was 17 µg/m3 and ranged from 0.1–68 µg/m3. The GM for the area measurements was 9.5 µg/m3. Differences between the GMs of the PBZ samples and area samples were not statistically different (P > 0.05). Neither the Occupational Safety and Health Administration (OSHA), NIOSH, nor the American Conference of Governmental Industrial Hygienists (ACGIH) have established occupational exposure limits (OEL) for DPM. However, the State of California, Department of Health Services lists a time-weighted average (TWA) OEL for DPM as elemental carbon (EC) exposure of 20 µg/m3. Five of 49 (10.2%) PBZ TWA measurements exceeded the 20 µg/m3 EC criterion. These measurements were collected on Sandmover and Transfer Belt (T-belt) Operators, Blender and Chemical Truck Operators, and Water Transfer Operators during hydraulic fracturing operations. Recommendations to minimize DPM exposures include elimination (locating diesel-driven pumps away from well sites), substitution, (use of alternative fuels), engineering controls using advanced emission control technologies, administrative controls (configuration of well sites), hazard communication, and worker training.

Field evaluation of onsite near real-time monitors for surface contamination by 5-fluorouracil

Objectives In order to produce near real-time onsite results to detect surface contamination by antineoplastic drugs, the National Institute for Occupational Safety and Health developed monitors for 5-fluorouracil, which use surface wiping and lateral flow immunoassay for measurement. The monitors were tested in the laboratory to assess the sensitivity of detection on laboratory-produced contaminated surfaces. A field evaluation to assess the capability of the monitors to make measurements in healthcare workplaces was carried out in collaboration with a medical device company and the results are presented in this report. Methods The 5-fluorouracil monitor was evaluated in areas where oncology drugs were prepared and administered to patients at five different hospitals. The levels of contamination measured with the monitors were compared to levels measured with liquid chromatography-tandem mass spectrometry. Results The 5-fluorouracil values measured with the liquid chromatography-tandem mass spectrometry ranged from 0 to over 200,000 ng/100 cm2. Measurements by the 5-fluorouracil monitors in the range 10–100 ng/100 cm2 correlated with the liquid chromatography-tandem mass spectrometry. Receiver operating characteristic curves developed for the data indicated that a positive limit of 22 ng/100 cm2 would give an acceptable level of false-positives while retaining most true-positive samples. If the liquid chromatography-tandem mass spectrometry measured greater than 100 ng/100 cm2, then the monitors also measured levels greater than 100 ng/100 cm2 for the majority of samples. Conclusion The data indicate that there are many areas in hospitals that are contaminated with 5-fluorouracil and the monitors will be useful in identifying this contamination.