Toxicological Effects of Inhaled Crude Oil Vapor.

PURPOSE OF REVIEW: The purpose of this review is to assess the toxicological consequences of crude oil vapor (COV) exposure in the workplace through evaluation of the most current epidemiologic and laboratory-based studies in the literature. RECENT FINDINGS: Crude oil is a naturally occuring mixture of hydrocarbon deposits, inorganic and organic chemical compounds. Workers engaged in upstream processes of oil extraction are exposed to a number of risks and hazards, including getting crude oil on their skin or inhaling crude oil vapor. There have been several reports of workers who died as a result of inhalation of high levels of COV released upon opening thief hatches atop oil storage tanks. Although many investigations into the toxicity of specific hydrocarbons following inhalation during downstream oil processing have been conducted, there is a paucity of information on the potential toxicity of COV exposure itself. This review assesses current knowledge of the toxicological consequences of exposures to COV in the workplace.

Biological effects of inhaled crude oil vapor. III. Pulmonary inflammation, cytotoxicity, and gene expression profile.

OBJECTIVE: Workers may be exposed to vapors emitted from crude oil in upstream operations in the oil and gas industry. Although the toxicity of crude oil constituents has been studied, there are very few in vivo investigations designed to mimic crude oil vapor (COV) exposures that occur in these operations. The goal of the current investigation was to examine lung injury, inflammation, oxidant generation, and effects on the lung global gene expression profile following a whole-body acute or sub-chronic inhalation exposure to COV. MATERIALS AND METHODS: To conduct this investigation, rats were subjected to either a whole-body acute (6 hr) or a sub-chronic (28 d) inhalation exposure (6 hr/d × 4 d/wk × 4 wk) to COV (300 ppm; Macondo well surrogate oil). Control rats were exposed to filtered air. One and 28 d after acute exposure, and 1, 28, and 90 d following sub-chronic exposure, bronchoalveolar lavage was performed on the left lung to collect cells and fluid for analyses, the apical right lobe was preserved for histopathology, and the right cardiac and diaphragmatic lobes were processed for gene expression analyses. RESULTS: No exposure-related changes were identified in histopathology, cytotoxicity, or lavage cell profiles. Changes in lavage fluid cytokines indicative of inflammation, immune function, and endothelial function after sub-chronic exposure were limited and varied over time. Minimal gene expression changes were detected only at the 28 d post-exposure time interval in both the exposure groups. CONCLUSION: Taken together, the results from this exposure paradigm, including concentration, duration, and exposure chamber parameters, did not indicate significant and toxicologically relevant changes in markers of injury, oxidant generation, inflammation, and gene expression profile in the lung.

Automated crude oil vapor inhalation exposure system.

Objective: Inhalation exposure systems are tools for delivering compounds (particles, vapors, and gases) under well-controlled conditions for toxicological testing. The objective of this project was to develop an automated computer-controlled system to expose small laboratory animals to precise concentrations of crude oil vapor (COV).Materials and Methods: Vapor from heated Deepwater Horizon surrogate oil was atomized into a fine mist then diluted with filtered air, then the air/droplet mixture was routed into an evaporation column with an high efficiency particulate air (HEPA) filter on its exit port. The HEPA filter was used to remove oil particles, thus ensuring only vapor would pass. The vapor was then introduced into a custom-built exposure chamber housing rats. A calibrated flame ionization detector was used to read the total volatile organic compounds (TVOC) in real time, and custom software was developed to automatically adjust the amount of oil entering the atomizer with a syringe pump. The software also controlled relative humidity and pressure inside the exposure chamber. Other exposure chamber environmental parameters, e.g. temperature and CO2 levels, were monitored. Four specific components within the COV were monitored during each exposure: benzene, toluene, ethylbenzene, and xylenes.Results: The TVOC vapor concentration control algorithm maintained median concentrations to within ±2 ppm of the target concentration (300 ppm) of TVOC during exposures lasting 6 h. The system could reach 90% of the desired target in less than 15 min, and repeat exposures were consistent and reproducible.Conclusion: This exposure system provided a highly automated tool for conducting COV inhalation toxicology studies.

Biological effects of inhaled crude oil vapor. II. Pulmonary effects.

Workers involved in oil exploration and production in the upstream petroleum industry are exposed to crude oil vapor (COV). COV levels in the proximity of workers during production tank gauging and opening of thief hatches can exceed regulatory standards, and several deaths have occurred after opening thief hatches. There is a paucity of information regarding the effects of COV inhalation in the lung. To address these knowledge gaps, the present hazard identification study was undertaken to investigate the effects of an acute, single inhalation exposure (6 h) or a 28 d sub-chronic exposure (6 h/d × 4 d/wk × 4 wks) to COV (300 ppm; Macondo well surrogate oil) on ventilatory and non-ventilatory functions of the lung in a rat model 1 and 28 d after acute exposure, and 1, 28 and 90 d following sub-chronic exposure. Basal airway resistance was increased 90 d post-sub-chronic exposure, but reactivity to methacholine (MCh) was unaffected. In the isolated, perfused trachea preparation the inhibitory effect of the airway epithelium on reactivity to MCh was increased at 90 d post-exposure. Efferent cholinergic nerve activity regulating airway smooth muscle was unaffected by COV exposure. Acute exposure did not affect basal airway epithelial ion transport, but 28 d after sub-chronic exposure alterations in active (Na+ and Cl¯) and passive ion transport occurred. COV treatment did not affect lung vascular permeability. The findings indicate that acute and sub-chronic COV inhalation does not appreciably affect ventilatory properties of the rat, but transient changes in airway epithelium occur.

Biological effects of inhaled crude oil. VI. Immunotoxicity.

Crude oil is an unrefined petroleum product that is a mixture of hydrocarbons and other organic material. Studies on the individual components of crude oil and crude oil exposure itself suggest it has immunomodulatory potential. As investigations of the immunotoxicity of crude oil focus mainly on ingestion and dermal exposure, the effects of whole-body inhalation of 300 ppm crude oil vapor [COV; acute inhalation exposure: (6 h × 1 d); or a 28 d sub-chronic exposure (6 h/d × 4 d/wk. × 4 wks)] was investigated 1, 28, and 90 d post-exposure in Sprague-Dawley rats. Acute exposure increased bronchoalveolar lavage (BAL) fluid cellularity, CD4+ and CD8+ cells, and absolute and percent CDllb+ cells only at 1 d post-exposure; additionally, NK cell activity was suppressed. Sub-chronic exposure resulted in a decreased frequency of CD4+ T-cells at 1 d post-exposure and an increased number and frequency of B-cells at 28 d post-exposure in the lung-associated lymph nodes. A significant increase in the number and frequency of B-cells was observed in the spleen at 1 d post-exposure; however, NK cell activity was suppressed at this time point. No effect on cellularity was identified in the BALF. No change in the IgM response to sheep red blood cells was observed. The findings indicate that crude oil inhalation exposure resulted in alterations in cellularity of phenotypic subsets that may impair immune function in rats.

Biological effects of inhaled crude oil vapor V. Altered biogenic amine neurotransmitters and neural protein expression.

Workers in the oil and gas industry are at risk for exposure to a number of physical and chemical hazards at the workplace. Chemical hazard risks include inhalation of crude oil or its volatile components. While several studies have investigated the neurotoxic effects of volatile hydrocarbons, in general, there is a paucity of studies assessing the neurotoxicity of crude oil vapor (COV). Consequent to the 2010 Deepwater Horizon (DWH) oil spill, there is growing concern about the short- and long-term health effects of exposure to COV. NIOSH surveys suggested that the DWH oil spill cleanup workers experienced neurological symptoms, including depression and mood disorders, but the health effects apart from oil dispersants were difficult to discern. To investigate the potential neurological risks of COV, male Sprague-Dawley rats were exposed by whole-body inhalation to COV (300 ppm; Macondo surrogate crude oil) following an acute (6 h/d × 1 d) or sub-chronic (6 h/d × 4 d/wk. × 4 wks) exposure regimen. At 1, 28 or 90 d post-exposure, norepinephrine (NE), epinephrine (EPI), dopamine (DA) and serotonin (5-HT) were evaluated as neurotransmitter imbalances are associated with psychosocial-, motor- and cognitive- disorders. Sub-chronic COV exposure caused significant reductions in NE, EPI and DA in the dopaminergic brain regions, striatum (STR) and midbrain (MB), and a large increase in 5-HT in the STR. Further, sub-chronic exposure to COV caused upregulation of synaptic and Parkinson's disease-related proteins in the STR and MB. Whether such effects will lead to neurodegenerative outcomes remain to be investigated.

Biological effects of crude oil vapor. IV. Cardiovascular effects.

Workers in the oil and gas extraction industry are at risk of inhaling volatile organic compounds. Epidemiological studies suggest oil vapor inhalation may affect cardiovascular health. Thus, in this hazard identification study we investigated the effects of inhalation of crude oil vapor (COV) on cardiovascular function. Male rats were exposed to air or COV (300 ppm) for 6 h (acute), or 6 h/day × 4 d/wk. × 4 wk. (sub-chronic). The effects of COV inhalation were assessed 1, 28, and 90 d post-exposure. Acute exposure to COV resulted in reductions in mean arterial and diastolic blood pressures 1 and 28 d after exposure, changes in nitrate-nitrite and H2O2 levels, and in the expression of transcripts and proteins that regulate inflammation, vascular remodeling, and the synthesis of nitric oxide (NO) in the heart and kidneys. The sub-chronic exposure resulted in a reduced sensitivity to α1-adrenoreceptor-mediated vasoconstriction in vitro 28 d post-exposure, and a reduction in oxidative stress in the heart. Sub-chronic COV exposure led to alterations in the expression of NO synthases and anti-oxidant enzymes, which regulate inflammation and oxidative stress in the heart and kidneys. There seems to be a balance between changes in the expression of transcripts associated with the generation of reactive oxygen species (ROS) and antioxidant enzymes. The ability of antioxidant enzymes to reduce or inhibit the effects of ROS may allow the cardiovascular system to adapt to acute COV exposures. However, sub-chronic exposures may result in longer-lasting negative health consequences on the cardiovascular system.

Biological effects of inhaled hydraulic fracturing sand dust VII. Neuroinflammation and altered synaptic protein expression.

Hydraulic fracturing (fracking) is a process used to recover oil and gas from shale rock formation during unconventional drilling. Pressurized liquids containing water and sand (proppant) are used to fracture the oil- and natural gas-laden rock. The transportation and handling of proppant at well sites generate dust aerosols; thus, there is concern of worker exposure to such fracking sand dusts (FSD) by inhalation. FSD are generally composed of respirable crystalline silica and other minerals native to the geological source of the proppant material. Field investigations by NIOSH suggest that the levels of respirable crystalline silica at well sites can exceed the permissible exposure limits. Thus, from an occupational safety perspective, it is important to evaluate the potential toxicological effects of FSD, including any neurological risks. Here, we report that acute inhalation exposure of rats to one FSD, i.e., FSD 8, elicited neuroinflammation, altered the expression of blood brain barrier-related markers, and caused glial changes in the olfactory bulb, hippocampus and cerebellum. An intriguing observation was the persistent reduction of synaptophysin 1 and synaptotagmin 1 proteins in the cerebellum, indicative of synaptic disruption and/or injury. While our initial hazard identification studies suggest a likely neural risk, more research is necessary to determine if such molecular aberrations will progressively culminate in neuropathology/neurodegeneration leading to behavioral and/or functional deficits.

Biological effects of inhaled hydraulic fracturing sand dust. II. Particle characterization and pulmonary effects 30 d following intratracheal instillation.

Hydraulic fracturing ("fracking") is used in unconventional gas drilling to allow for the free flow of natural gas from rock. Sand in fracking fluid is pumped into the well bore under high pressure to enter and stabilize fissures in the rock. In the process of manipulating the sand on site, respirable dust (fracking sand dust, FSD) is generated. Inhalation of FSD is a potential hazard to workers inasmuch as respirable crystalline silica causes silicosis, and levels of FSD at drilling work sites have exceeded occupational exposure limits set by OSHA. In the absence of any information about its potential toxicity, a comprehensive rat animal model was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems (Fedan, J.S., Toxicol Appl Pharmacol. 00, 000-000, 2020). The present report, part of the larger investigation, describes: 1) a comparison of the physico-chemical properties of nine FSDs, collected at drilling sites, and MIN-U-SIL® 5, a reference silica dust, and 2) a comparison of the pulmonary inflammatory responses to intratracheal instillation of the nine FSDs and MIN-U-SIL® 5. Our findings indicate that, in many respects, the physico-chemical characteristics, and the biological effects of the FSDs and MIN-U-SIL® 5 after intratracheal instillation, have distinct differences.