Development of occupational exposure limits for the Hanford tank farms.

Production of plutonium for the United States' nuclear weapons program from the 1940s to the 1980s generated 53 million gallons of radioactive chemical waste, which is stored in 177 underground tanks at the Hanford site in southeastern Washington State. Recent attempts to begin the retrieval and treatment of these wastes require moving the waste to more modern tanks and result in potential exposure of the workers to unfamiliar odors emanating from headspace in the tanks. Given the unknown risks involved, workers were placed on supplied air respiratory protection. CH2MHILL, the managers of the Hanford site tank farms, asked an Independent Toxicology Panel (ITP) to assist them in issues relating to an industrial hygiene and risk assessment problem. The ITP was called upon to help determine the risk of exposure to vapors from the tanks, and in general develop a strategy for solution of the problem. This paper presents the methods used to determine the chemicals of potential concern (COPCs) and the resultant development of screening values and Acceptable Occupational Exposure Limits (AOELs) for these COPCs. A total of 1826 chemicals were inventoried and evaluated. Over 1500 chemicals were identified in the waste tanks headspaces and more than 600 of these were assigned screening values; 72 of these compounds were recommended for AOEL development. Included in this list of 72 were 57 COPCs identified by the ITP and of these 47 were subsequently assigned AOELs. An exhaustive exposure assessment strategy was developed by the CH2MHILL industrial hygiene department to evaluate these COPCs.

Percutaneous absorption of 2,6-di-tert-butyl-4-nitrophenol (DBNP) in isolated perfused porcine skin.

DBNP (2,6-di-tert-butyl-4-nitrophenol) has been reported as a potential contaminant in submarines. This yellow substance forms when lubrication oil mist containing the antioxidant additive 2,6-di-tert-butylphenol passes through an electrostatic precipitator and is nitrated. Percutaneous absorption of 14C-DBNP was assessed in the isolated perfused porcine skin flap (IPPSF). Four treatments were studied (n=4 flaps/treatment): 40.0 microgram/cm(2) in 100% ethanol; 40.0 microgram/cm(2) in 85% ethanol/15% H(2)O; 4.0 microgram/cm(2) in 100% ethanol; and 4.0 microgram/cm(2) in 85% ethanol/15% water. DBNP absorption was minimal across all treatment groups, with the highest absorption detected being only 1.08% applied dose in an aqueous ethanol group. The highest mass of 14C-DBNP absorbed was only 0.5 microgram. The majority of the applied dose remained on the surface of the skin. This suggests that there is minimal dermal exposure of DBNP when exposed topically to skin.

The utilization of risk assessments in tactical command decisions.

Traditional risk assessments (as delineated by regulatory agencies) use health outcome endpoints of interest to society as a whole, and are based on broad assumptions about the demographics of the potentially exposed populations and the routes of exposure. Immediacy of impact is not normally a major consideration. In tactical situations, the commander must balance considerations of short-term health effects against mission accomplishment. Often the commander will decide to accept a risk that would not be considered under other circumstances. The traditional tools of human-health and environmental risk assessment may be used, but the risk levels and projected consequences must be adapted to the tactical scenario (i.e. the performance decrement associated with a short-term exposure tactical operation vs. the long-term health out-come for an exposed population under 'normal conditions'). Risk assessors and health professionals must learn to articulate risk in terms that the tactical commander can place in his operational risk management (ORM) process. The process may require that the commander weigh non-health related mission critical considerations against health outcome issues. This presentation is intended to begin a dialogue that will lead to a harmonization of the use of risk assessment tools and their application in ORM as seen by tactical commanders, and a clarification of the strengths and limits of their utility in such applications.

Effect of method of euthanasia on sperm motility of mature Sprague-Dawley rats.

Euthanasia is one of the most commonly performed procedures in laboratory animal settings. The method of euthanasia may affect experimental results in studies using animals and must be compatible with research objectives including subsequent tissue analyses. Our present study was performed to evaluate the effects of 7 euthanasia methods on sperm motility in mature rats. Rats were euthanized using CO2, 2 commercially available euthanasia solutions (Beuthanasia-D and Sleepaway), and 4 volatile anesthetics (enflurane, halothane, isoflurane, and sevoflurane). Rats euthanized by rapid decapitation alone served as negative controls, and a-chlorohydrin-treated rats euthanized by rapid decapitation were positive controls for sperm impairment. For 5 of these methods, we also measured time to ataxia, recumbency, respiratory arrest, and no auscultable heartbeat. Immediately after euthanasia of each rat, distal caudal epididymides were removed; 1 was processed for automated sperm motility analysis, and the other was frozen for subsequent concentration analysis. Time to all measured parameters was less for volatile anesthetics than for Beuthanasia-D. Times to last respiration and no heartbeat were less for halothane and isoflurane than for enflurane and sevoflurane. Percentage motile sperm did not differ significantly between methods. Percentage progressively motile sperm did not vary significantly between methods except for Beuthanasia-D, for which it was significantly less than the negative control value. Specific sperm motion parameters for each euthanasia method except CO2 and Sleepaway varied significantly from the negative control. Our results indicate that the method of euthanasia is an important consideration when rat sperm motility parameters must be evaluated.

Evaluation of the effect of implanted depleted uranium on male reproductive success, sperm concentration, and sperm velocity.

Depleted uranium (DU) projectiles have been used in battle in Iraq and the Balkans and will continue to be a significant armor-penetrating munition for the US military. As demonstrated in the Persian Gulf War, battle injury from DU projectiles and shrapnel is a possibility, and removal of embedded DU fragments from the body is not always practical because of their location in the body or their small size. Previous studies in rodents have demonstrated that implanted DU mobilizes and translocates to the gonads, and natural uranium may be toxic to spermatazoa and the male reproductive tract. In this study, the effects of implanted DU pellets on sperm concentration, motility, and male reproductive success were evaluated in adult (P1) Sprague-Dawley rats implanted with 0, 12, or 20, DU pellets of 1x2 mm or 12 or 20 tantalum (Ta) steel pellets of 1x2 mm. Twenty DU pellets of 1x2 mm (760 mg) implanted in a 500-g rat are equal to approximately 0.2 pound of DU in a 154-lb (70-kg) person. Urinary analysis found that male rats implanted with DU were excreting uranium at postimplantation days 27 and 117 with the amount dependent on dose. No deaths or evidence of toxicity occurred in P1 males over the 150-day postimplantation study period. When assessed at postimplantation day 150, the concentration, motion, and velocity of sperm isolated from DU-implanted animals were not significantly different from those of sham surgery controls. Velocity and motion of sperm isolated from rats treated with the positive control compound alpha-chlorohydrin were significantly reduced compared with sham surgery controls. There was no evidence of a detrimental effect of DU implantation on mating success at 30-45 days and 120-145 days postimplantation. The results of this study suggest that implantation of up to 20 DU pellets of 1x2 mm in rats for approximately 21% of their adult lifespan does not have an adverse impact on male reproductive success, sperm concentration, or sperm velocity.

Disposition and pharmacokinetics of a lubricant contaminant, 2,6-di-tert-butyl 4-nitrophenol, in grafted human skin.

Disposition and uptake/elimination profiles of topical 2,6-di-t-butyl, 4-nitrophenol (DBNP), the nitrated metabolite of an antioxidant additive of lubricant and hydraulic fluids was quantified in human skin grafted on athymic mice after a single topical 75 microg dose in corn oil. DBNP was quantified throughout the stratum corneum (SC), epidermis (E) and dermis (D) in punch biopsies collected from treated skin 0.5, 1, 2, 4, 8 and 24 h after application. SC samples were harvested from the treated skin with 20 adhesive discs. E and D were generated from the biopsy using a manual sectioning method. Detectable DBNP concentrations were measured in all skin compartments at all time points investigated. The Cmax of DBNP in SC was 1663 +/- 602 microg cm(-3), and approximately 30 and approximately 300 fold greater than the Cmax for E and D, respectively. Tmax occurred at 1.0, 0.5 and 1.0 in the SC, E and D, respectively. Over a 24 h interval (AUC0-24 h) there was 52 and 520 fold more DBNP in the SC than E and D, respectively. The elimination half-life of DBNP was 11 h from the SC and 9 h from both E and D. Thus, DBNP was quickly absorbed into the outermost layer of skin and established a steep concentration profile through human skin. The data are consistent with the vast majority of DBNP remaining on the surface (77%) or within human skin (15%) in vivo with only 0.2% of the DBNP dose quantified in the systemic blood circulation.

Disposition of 2,6-di-tert-butyl-4-nitrophenol (DBNP), a submarine atmosphere contaminant, in male Sprague-Dawley rats.

The phenol 2,6-di-tert-butyl-4-nitrophenol (DBNP) is a contaminant found onboard submarines and is formed by the nitration of an antioxidant present in turbine lubricating oil TEP 2190. DBNP has been found on submarine interior surfaces, on eating utensils and dishes, and on the skin of submariners. DBNP exposure is a potential health concern because it is an uncoupler of mitochondrial oxidative phosphorylation. Adult male rats were dosed once by oral gavage with 15 or 40 mg/kg DBNP mixed with 14C-DBNP in kanola oil and 0.8% v/v DMSO (n = 16/group). The distribution of 14C in major tissues was measured over time for up to 240 h post-dose. Unexpectedly, 6/16 (40%) of the rats gavaged with 40 mg/kg DBNP died within 24 h of dosing. Prostration, no auditory startle response, reduced locomotor activity, and muscular rigidity persisted in survivors for up to 8 days after dosing. For animals dosed with 15 mg/kg DBNP, radioactivity levels were significantly elevated in the following tissues 24h after dosing: fat>>>liver>kidneys>heart>lungs>brain>striated muscle>spleen. Radioactivity levels were elevated for fat, liver, kidney, heart, and lungs of animals euthanized 144 h post-dosing and in the liver of animals euthanized 240 h post-dosing. These findings suggest that DBNP may accumulate in the body as a result of continuous or repeat exposures of short interval to DBNP.

Airway reactivity response to aged carbon-graphite/epoxy composite material smoke.

Exposure of naïve guinea pigs for a total of 30 min to aged smoke from pyrolysis of 5, 10 and 100 g of carbon-graphite/epoxy-advanced composite material (cgeCM) elicited changes in the ventilation and breathing pattern reminiscent of an acute, asthmatic episode. The severity of these responses was dose related. Although breathing pattern changes were not definitive of stimulation by a single type of respiratory irritant, non-dimensional indices derived from breath structure appeared to be characteristic of bronchoconstriction possibly complicated by CO(2)-stimulated ventilation. The highest exposure concentration also elicited convulsions in the animals, which may or may not be related to the airway reactivity (AR) response. Upon treatment with fresh air, breathing returned to normal. However, this recovery was transient with some respiratory parameters returning to abnormal levels, possibly indicating a rebound or delayed component of the response. Filtration of particulate material from the smoke moderated but did not eliminate the AR response. Animals exposed to diluted smoke from the pyrolysis of 2 g of cgeCM showed no remarkable changes in breathing or ventilation, suggesting that there may be a threshold for aged cgeCM smoke-elicited AR response.

Exposure assessment and the health of deployed forces.

The risk assessment process is a critical function for military Deployment Toxicology research objectives, emphasizing improved health protection of deployed forces. Reliable risk assessment methodology is essential for decision making related to risk reduction procedures during combat deployment, as well as during routine occupational activities. Such decision making must be based upon quality science that both guides sound judgments in risk characterization and management, and provides necessary health protection tools. The health and fitness of deployed forces must be considered for both acute and long-term issues. Exposure assessment specifies populations that might be exposed to injurious agents, identifies routes of exposure, and estimates the magnitude, duration, and timing of the doses that personnel may receive as a result of their exposure. Acute or short-term catastrophic risks for deployed forces are of immediate concern and must be addressed on a risk prioritization basis using Operational Risk Management (ORM) procedures. However, long-term effects of exposure to the same agents must be considered as part of the overall health concerns for deployed forces. In response to these needs, a number of military, federal government, academic and private sector organizations are currently developing new classes of biologically-based biosensors with the programmed capacity to detect the presence of virtually any environmental chemical or biological stressor with the capacity to induce health consequences in deployed personnel. A major objective of this engineering effort is development of biosensor systems that detect novel (previously unresearched) chemical or biological agents that might be used during international combat or terrorist attacks to induce acute or long-term health effects on military or civilian populations. A large portion of the discussion in this paper is devoted to describing the development, testing, and implementation of tissue-based biosensors (TBBs) that utilize small samples of living tissue from laboratory small animals for a wide range of human risk assessment applications.

Effect of Navy chaff release on aluminum levels in an area of the Chesapeake Bay.

The U.S. Navy uses aluminized glass chaff as a passive countermeasure for radar-guided threats to aircraft and surface ships. Over the last 25 years, several hundred thousand pounds of aluminized chaff have been released during flight operations over a training area on the Chesapeake Bay. There is concern that these releases have resulted in the accumulation of significant amounts of aluminum in the soil and sediment of this training area. This study compares the exchangeable and monomeric aluminum content of sediment within the affected area with that of samples taken from outside the training area. We found a less than twofold increase in the content of organic monomeric aluminum in samples taken from the affected area versus background samples, whereas inorganic monomeric aluminum concentrations within the affected area were significantly lower than background. These results suggest that chaff releases have not resulted in a significant accumulation of aluminum in this training area.

Assessment of the aquatic and terrestrial toxicity of five biodegradable polymers.

Radiofrequency countermeasures (i.e., chaff) may be released by fighter jets during tactical countermeasures training. Chaff cartridges, pistons, and endcaps (i.e., chaff dispenser materials), all currently made of styrene, are also released into the environment. Accumulation of chaff dispenser materials in the environment is a concern of the Department of Defense. The US Navy is exploring the possibility of constructing degradable chaff dispenser components made of biodegradable polymers. Five polymers are being considered. Degradability and toxicity tests are two of several criteria being used to evaluate various available biodegradable options. Dissolution products from four of five polymers being considered were toxic to aquatic organisms with LC50s/LOELs ranging between 1.24 and 731.30 mg total organic concentration/L. Supernatant from dissolving a 90:10 polyester amide/polyvinyl alcohol copolymer in water for 24h inhibited shoot growth of Brassica rappa and Lepidium sativum. Since our results were obtained using fractions of saturated degradable polymer solutions (1 or 10 g/L), we conclude that the tested degradable polymers were of low toxicity to the seven aquatic organisms and two terrestrial plant species used in our assays. However, our characterization of the toxicity of these degradable polymers may not be applicable to all species or environmental situations. Information gained from these studies will be used for making decisions on which polymers should be used in the engineering of environmentally friendly chaff dispenser cartridges, pistons, and endcaps.

Analysis of rat testicular protein expression following 91-day exposure to JP-8 jet fuel vapor.

We analyzed protein expression in preparations from whole testis in adult male Sprague-Dawley rats exposed for 6 h/d for 91 consecutive days to jet propulsion fuel-8 (JP-8) in the vapor phase (0, 250, 500, or 1000 mg/m(3) +/- 10%), simulating a range of possible human occupational exposures. Whole body inhalation exposures were carefully controlled to eliminate aerosol phase, and subjects were sacrificed within 48 h postexposure. Organ fractions were solubilized and separated via large-scale, high resolution two-dimensional electrophoresis, and gel patterns scanned, digitized and processed for statistical analysis. Seventy-six different testis proteins were significantly increased or decreased in abundance in vapor-exposed groups, compared to controls, and dose-response profiles were often nonlinear. A number of the proteins were identified by peptide mass fingerprinting and related to histopathological or physiological deficits shown in previously published studies to occur with repeated exposure to hydrocarbon fuels or solvents. These results demonstrate a significant effect of JP-8 exposure on protein expression, particularly in protein expression in the rodent testis, and suggest that a 91 d exposure to jet fuel vapor induces changes of equal or greater magnitude to those reported previously for shorter duration JP-8 aerosol exposures.