Effects of Aerosol-Vapor JP-8 Jet Fuel on the Functional Observational Battery,and Learning and Memory in the Rat

To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.     

Intermittent binge alcohol exposure during the periadolescent period induces spatial working memory deficits in young adult rats

Human and animal studies suggest adolescence is a period of heightened sensitivity to adverse cognitive sequelae of alcohol exposure. The present study assessed the effects of intermittent binge ethanol intoxication during the periadolescent period of Wistar rats on subsequent performance in a Morris water maze spatial navigation task. On postnatal days 32-56, rats were exposed to ethanol or air 3 days/week via vapor inhalation chambers. Acquisition of spatial navigation was assessed beginning 5 days after the final day of exposure, with 3 days of training in the Morris Water maze (four trials per day spaced at 90-s intertrial intervals [ITIs]). Rats were placed into the water maze at one of four positions along the perimeter, with a different release position to begin each trial. A probe trial assessed retention of platform location on the day after the final set of training trials. Four days after this probe trial, rats entered a working memory phase in which the platform was in a new location each day and a variable ITI of 1, 2, or 4h was inserted between Trials 1 and 2; Trials 3 and 4 followed at 90-s intervals after Trial 2 on each day. The "savings" in latency to find the platform and distance traveled before finding it from Trial 1 to Trial 2 on each day served as an index of working memory. Ethanol-exposed rats showed similar acquisition of spatial navigation as control rats during training, as well as similar retention of platform location during the probe trial. However, rats exposed to average blood alcohol level (BAL) >200mg% showed accelerated forgetting, with decreased retention of platform location at the 2-h ITI (P<.05), compared to control rats. Therefore, a 4-week history of intermittent ethanol exposure at BAL in excess of 200mg% during periadolescence led to a working memory deficit in young adult rats, demonstrated by accelerated forgetting of novel information. These behavioral data are consistent with findings from adolescent human studies, indicating that binge-style alcohol exposure during the periadolescent stage of development is associated with deficits in retention of information.     

Substance P as prophylaxis for JP-8 jet fuel-induced immunotoxicity.

Previous studies have shown that short-term, low-concentration JP-8 exposure had significant effects on the immune system that persisted for extended periods of time. It was found that administration of aerosolized substance P (SP) was able to protect exposed animals from JP-8-induced immune changes, whereas administration of SP antagonists compounded the deleterious effects ofjet fuel exposure. Thus, SP administration appears to be a relatively simple and efficient means to reverse the immunotoxicity due to hydrocarbon exposure. In the current study, aerosolized SP was analyzed for its potential prophylactic ability to counteract JP-8-induced immunotoxicity. It was observed that concentrations as low as 1 nM were effective in ameliorating the effects of JP-8 exposure on the immune system. SP administered before JP-8 exposure could prophylactically protect both the spleen and thymus from significant organ weight loss, but could not completely restore immune cell numbers to normal, baseline levels. Furthermore, SP treatment could be delayed as long as 1 h postexposure and reverse the effects of jet fuel exposure on immune organ weight loss and immune cell recovery. Significantly, SP could be given 15 min pre-JP-8 exposure but neither 1 nor 6 h pre-JP-8 exposure, and prevent immune dysfunction as measured in mitogenesis assays. However, SP could be delayed up to 6 h post-JP-8 exposure and still almost completely restore immune function. Thus, SP appears able to both prevent and reverse the immunotoxicological effects associated with JP-8 exposure. These results also provide insight into the manner in which JP-8 jet fuel mediates its effects on the immune system.     

Effects of different exercise protocols on ethanol-induced spatial memory impairment in adult male rats

Chronic ethanol consumption is often accompanied by numerous cognitive deficits and may lead to long-lasting impairments in spatial learning and memory. The aim of the present study was to evaluate the therapeutic potential of regular treadmill exercise on hippocampal-dependent memory in ethanol-treated rats. Spatial memory was tested in a Morris Water Maze task. Adult male Wistar rats were exposed to ethanol (4 g/kg, 20% v/v for 4 weeks) and effects of three exercise protocols (pre-ethanol, post-ethanol and pre-to-post-ethanol treatment) were examined. Results showed that ethanol exposure resulted in longer escape latencies during the acquisition phase of the Morris Water Maze task. Moreover, all three exercise protocols significantly decreased the latency to locate the hidden platform. During the probe trial, ethanol led to decreased time spent in the target quadrant. In contrast, performance on the probe trial was significantly better in the rats that had done the post- and pre-to-post-ethanol, but not pre-ethanol, exercises. These findings suggest that treadmill running can attenuate the adverse effects of chronic ethanol exposure on spatial memory, and may serve as a non-pharmacological alcohol abuse treatment.     

乐果亚慢性染毒对大鼠谷氨酸递质系统和学习记忆的影响

目的探讨有机磷农药乐果亚慢性染毒对大鼠学习记忆功能的影响及对中枢兴奋性氨基酸神经递质系统的可能作用。方法48只成年雄性SD大鼠随机分成4组，每组12只。对3个实验组以乐果经口灌胃（5、10和20mg／kg），每周5d，每天1次，共13周；对照组给予等体积的生理盐水。染毒结束，每组随机取6只大鼠在Morris水迷宫中检测动物学习记忆功能的改变情况；其余大鼠断头处死进行生化测定。使用硫代乙酰胆碱一二硫代双硝基甲酸（Asch．DTNB）法测定海马中乙酰胆碱酯酶（AChE）活力；用反相高效液相色谱荧光法测定海马中谷氨酸含量；用配体受体结合实验测定N-甲基-D-天门冬氨酸（NMDA）受体的Bmax和Kd值。结果大鼠定位航行实验中，随着训练期的增加，各组动物逃避潜伏期明显缩短；中、高剂量乐果染毒组的潜伏期比对照组长，差异有统计学意义（P〈0．05）。空间探索实验中，高剂量组与对照组相比，穿越平台位置的次数明显减少，差异有统计学意义（P〈0．05）。动物染毒后，低、中、高染毒组大鼠海马AChE活力分别为对照组的77．9％、62．8％和42．1％，差异有统计学意义，存在剂量一效应关系（P〈0．01）。中、高剂量组大鼠海马分区谷氨酸含量与对照组相比增加134．5％、132．9％．差异有统计学意义（P〈0．05）；中、高剂量组NMDA受体Bmax值与对照组相比降低21．2％、23．2％，差异有统计学意义（P〈0．05）；各剂量组受体Kd值增加22．2％-33．1％，且高剂量组与对照组比较，差异均有统计学意义（P〈O．05）。大鼠的空间记忆能力下降与海马中NMDA受体的亲和力下降在统计学上有相关关系（P〈O．05）。结论乐果亚慢性染毒可引起大鼠中枢兴奋性氨基酸神经递质含量及NMDA受体密度和亲和力的改变，并在降低大鼠的学习记忆功能中可能发挥一定的作用。     

Reversal learning after prenatal or early postnatal alcohol exposure in juvenile and adult rats.

Learning tasks that require the reversal of a previously learned contingency are disrupted in animals and humans exposed to alcohol during the perinatal period. The current experiments examined how varying the time of alcohol exposure and the age at which subjects were tested would affect the expression of reversal deficits in a T-maze task. Groups of rats were exposed to alcohol from gestational day (GD) 8 to GD20 or from postnatal day (PN) 4 to PN9, and then tested in a spatial reversal task at either PN28 or PN63. Results indicate that exposure to alcohol during the prenatal period did not lead to substantial dose-dependent reversal learning deficits in males or females at either age tested. However, exposure to alcohol during the early postnatal period, a period that corresponds to the third trimester in human neural development, selectively disrupted reversal learning performance in male rats at PN28 but not PN63. Statistically significant sex differences were seen when subjects were tested at PN63. These results demonstrate how the timing of alcohol exposure leads to variability in the age-dependent expression of learning deficits associated with fetal alcohol effects.     

Scopolamine does not differentially affect Morris maze performance in adult rats exposed prenatally to alcohol

Rats exposed prenatally to alcohol have shown deficits in spatial learning in radial-arm and Morris mazes. Prenatal exposure to alcohol in rats has also been shown to alter central nervous system (CNS) cholinergic function. Since cholinergic dysfunction disrupts spatial learning in normal rats, the present experiment assessed the role of putative prenatal alcohol-induced cholinergic dysfunction in spatial learning in rats. Pregnant rats were fed alcohol via liquid diet from gestation day 6 to 20. Control dams were pair-fed liquid diet without alcohol or fed ad lib lab chow and water. Group housed adult male and female offspring (postnatal days 110 to 135) were given scopolamine-HCl (o, 0.5, or 1.0 mg/kg/day) and tested in a Morris maze, with four trials per day for four days. A 15-s probe trial preceded testing on days 2–4. On day 5, the rats were given four trials to learn a new platform location. Scopolamine produced dose-dependent increases in latency to find the platform for all groups. There were no significant differences among prenatal treatment groups in scopolamine-induced shifts in performance. The results did not support the hypothesis that prenatal alcohol-induced CNS cholinergic dysfunction is related to spatial learning performance in these rats.     

砷对仔代大鼠神经行为和学习记忆功能影响

目的研究饮水砷暴露对大鼠仔鼠神经行为发育和学习记忆功能的影响.方法雌性大鼠于受孕后第6d开始以自由饮水方式分别暴露于10,50和100mg/L的NaAsO2水溶液,连续染毒直到仔鼠出生后第42d.观察砷对仔代大鼠生理发育、神经行为发育及学习记忆能力的影响.结果 100mg/L砷剂量组仔鼠从出生后第12d起身长、体重明显低于对照组,但张耳、开眼、长毛、出牙、抬头、爬行、站立和行走等生理发育指标与对照组相比差异无统计学意义.在神经行为测试中,100mg/L砷剂量组仔鼠尾部悬挂、听觉惊愕和视觉定位等指标阳性率显著低于对照组,出现神经行为发育迟缓.方位水迷宫实验中,各砷暴露组仔鼠在记忆获得测试和记忆保留测试中能正确寻找隐蔽平台所需训练次数显著多于对照组,说明砷对仔鼠短时记忆和长时记忆均有一定影响.结论饮水砷暴露可对仔鼠神经行为和学习记忆产生毒性作用.     

极低频弱电磁场对大鼠学习记忆的影响

目的 研究极低频弱电磁场短期及长期照射对大鼠学习记忆的影响。方法 用Helmholtz线圈产生50Hz,强度连续可调的均匀弱电磁场(0．1、1．2、1．6 mT),分别对青龄(2～3月)及大龄(18个月)SD大鼠照射10d～8个月,通过Morris水迷宫实验检测电磁场照射后大鼠逃避潜伏期和穿环系数以反应定位航行和空间探索行为功能的变化。结果 青龄大鼠照射10d,0．1、1．2、1．6 mT组的逃避潜伏期缩短,穿环系数增大,1．2、1．6 mT组与对照组差异有显著性;1．6 mT组停止照射30d后逃避潜伏期和穿环系数与对照组差异无显著性;1．2 mT组连续照射90d,潜伏期延长,穿环系数减少,与对照组差异有显著性。大龄大鼠0．1 mT组照射10d,潜伏期变化不显著;照射4个月后潜伏期延长,照射8个月后潜伏期延长更显著。结论 50Hz弱电磁场对青龄大鼠短期电磁场照射可以暂时促进学习记忆,但长期照射则抑制学习记忆;对大龄大鼠长期弱照射明显抑制学习记忆能力。     

JP-8 jet fuel exposure potentiates tumor development in two experimental model systems

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and prostaglandin E2 (PGE2). Thus, it was of interest to determine if jet fuel exposure might promote tumor growth and metastasis. The syngeneic B16 tumor model was used for these studies. Animals were injected intravenously with tumor cells, and lung colonies were enumerated. Animals were also examined for metastatic spread of the tumor. Mice were either exposed to 1000 mg/m3 JP-8 (1 h/ day) for 7 days before tumor injection or were exposed to JP-8 at the time of tumor injection. All animals were killed 17 days after tumor injection. In the present study, JP8 exposure potentiated the growth and metastases of B16 tumors in an animal model. Exposure of mice to JP-8 for 1 h/day before tumor induction resulted in an approximately 8.7-fold increase in tumors, whereas those mice exposed to JP8 at the time of tumor induction had a 5.6-fold increase in tumor numbers. Thus, low concentration JP-8 jet fuel exposures have significant immune suppressive effects on the immune system that can result in increased tumor formation and metastases. We have now extended the observations to an experimental subcutaneous tumor model. JP8 exposure at the time of tumor induction in this model did not affect the growth of the tumor. However, JP8-exposed, tumor-bearing animals died at an accelerated rate as compared with air-exposed, tumor-bearing mice.     

Effects of short-term JP-8 jet fuel exposure on cell-mediated immunity

The U.S. Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Exposure to environmental toxicants such as JP-8 may have significant effects on host physiology. Jet fuel exposure has been shown to cause human liver dysfunction, abnormal electroencephalograms, shortened attention spans, and decreased sensorimotor speed. Previous studies have shown that short-term, low-concentration JP-8 exposure had significant effects on the immune system; e.g., decreased viable immune cell numbers, decreased immune organ weights, and loss of immune function that persisted for extended periods of time (i.e., up to 4 weeks post-exposure). In the current study, an in-depth analysis of the effects of JP-8 exposure on cellular immunity was performed. Short-term (7 days, 1 h/day), low-concentration (1000 mg/m3) exposures were conducted in mice, and T cell and natural killer (NK) cell functions were analyzed 24 h after the last exposure. The exposure regimen was found to almost completely ablate NK cell function, as well as significantly suppress the generation of lymphokine-activated killer (LAK) cell activity. Furthermore, JP-8 exposure suppressed the generation of cytotoxic T lymphocyte (CTL) cells from precursor T cells, and inhibited helper T cell activity. These findings demonstrate that JP-8 jet fuel exposure has significant detrimental effects on immune functions of exposed individuals. JP-8 jet fuel should be considered a potential and significant immunotoxicant. Chronic exposure to JP-8 may have serious implications to the long-term health of exposed individuals.     

Low lead exposure during foetal and early postnatal life impairs passive avoidance learning in adulthood in rats

This follow-up study investigated the effects of low-level lead exposure during prenatal and early postnatal period on learning and memory in rats immediately after exposure has ceased at weaning and later in their adulthood. Male Wistar-derived rats were exposed to lead (as 0.2 % lead acetate solution) through their mothers during pregnancy and lactation until they were weaned. Mothers of control rats were given tap water during pregnancy and lactation. All pups were weaned on tap water at 21 days of age and were followed up until 120 days old. Low-level lead exposure did not affect their body weight at any time during the experiment. Blood lead in the exposed rats was significantly higher on postnatal day 22 and dropped to control values by day 120. Passive avoidance test showed impaired memory retention in the exposed rats on postnatal days 25 and 120. This suggests that exposure to low-lead levels during foetal and early postnatal development of brain tissue can cause memory impairment that lasts into adulthood.     

Personal exposure to JP-8 jet fuel vapors and exhaust at air force bases

JP-8 jet fuel (similar to commercial/international jet A-1 fuel) is the standard military fuel for all types of vehicles, including the U.S. Air Force aircraft inventory. As such, JP-8 presents the most common chemical exposure in the Air Force, particularly for flight and ground crew personnel during preflight operations and for maintenance personnel performing routine tasks. Personal exposure at an Air Force base occurs through occupational exposure for personnel involved with fuel and aircraft handling and/or through incidental exposure, primarily through inhalation of ambient fuel vapors. Because JP-8 is less volatile than its predecessor fuel (JP-4), contact with liquid fuel on skin and clothing may result in prolonged exposure. The slowly evaporating JP-8 fuel tends to linger on exposed personnel during their interaction with their previously unexposed colleagues. To begin to assess the relative exposures, we made ambient air measurements and used recently developed methods for collecting exhaled breath in special containers. We then analyzed for certain volatile marker compounds for JP-8, as well as for some aromatic hydrocarbons (especially benzene) that are related to long-term health risks. Ambient samples were collected by using compact, battery-operated, personal whole-air samplers that have recently been developed as commercial products; breath samples were collected using our single-breath canister method that uses 1-L canisters fitted with valves and small disposable breathing tubes. We collected breath samples from various groups of Air Force personnel and found a demonstrable JP-8 exposure for all subjects, ranging from slight elevations as compared to a control cohort to > 100 [mutilpe] the control values. This work suggests that further studies should be performed on specific issues to obtain pertinent exposure data. The data can be applied to assessments of health outcomes and to recommendations for changes in the use of personal protective equipment that optimize risk reduction without undue impact on a mission.     

Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel aerosol inhalation

Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months; adult, 12 months; half in each age group) were randomly assigned to the exposure or control groups. Mice were nose-only exposed to room air or atmospheres of 1000 mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary mechanics, respiratory permeability, lavaged cell profile, and chemical mediators in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8 jet fuel had similar values with regards to increased lung dynamic compliance, lung permeability, BALF cell count, and decreased PGE2. However, there were several different responses between the young-versus-adult mice with respect to BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8 jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory mechanisms leading to lung injury and dysfunction in the younger-versus-adult mice.     

Effects of in utero JP-8 jet fuel exposure on the immune systems of pregnant and newborn mice

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. In the present study, the effects of in-utero JP-8 jet fuel exposure in mice were examined to ascertain any potential effects of jet fuel exposure on female personnel and their offspring. Exposure by the aerosol route (at 1000 mg/m3 for 1 h/day; similar to exposures incurred by flight line personnel) commencing during the first (d7 to birth) or last (d15 to birth) trimester of pregnancy was analyzed. It was observed that even 6-8 weeks after the last jet fuel exposure that the immune system of the dams (mother of newborn mice) was affected (in accordance with previous reports on normal mice). That is, thymus organ weights and viable cell numbers were decreased, and immune function was depressed. A decrease in viable male offspring was found, notably more pronounced when exposure started during the first trimester of pregnancy. Regardless of when jet fuel exposure started, all newborn mice (at 6-8 weeks after birth) reported significant immunosuppression. That is, newborn pups displayed decreased immune organ weights, decreased viable immune cell numbers and suppressed immune function. When the data were analyzed in relation to the respective mothers of the pups the data were more pronounced. Although all jet fuel-exposed pups were immunosuppressed as compared with control pups, male offspring were more affected by jet fuel exposure than female pups. Furthermore, the immune function of the newborn mice was directly correlated to the immune function of their respective mothers. That is, mothers showing the lowest immune function after JP-8 exposure gave birth to pups displaying the greatest effects of jet fuel exposure on immune function. Mothers who showed the highest levels of immune function after in-utero JP-8 exposure gave birth to pups displaying levels of immune function similar to controls animals that had the lowest levels of immune function. These data indicated that a genetic component might be involved in determining immune responses after jet fuel exposure. Overall, the data showed that in-utero JP-8 jet fuel exposure had long-term detrimental effects on newborn mice, particularly on the viability and immune competence of male offspring.     

JP-8 jet fuel exposure rapidly induces high levels of IL-10 and PGE2 secretion and is correlated with loss of immune function

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has demonstrated that JP-8 exposure is immunosuppressive. In the present study, the potential mechanisms for the effects of JP-8 exposure on the immune system were investigated. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and prostaglandin E2 (PGE2). JP-8 exposure rapidly induced a persistently high level of serum IL-10 and PGE2 at an exposure concentration of 1000 mg/m3. IL-10 levels peaked at 2 h post-JP-8 exposure and then stabilized at significantly elevated serum levels, while PGE2 levels peaked after 2-3 days of exposure and then stabilized. Elevated IL-10 and PGE2 levels may at least partially explain the effects of JP-8 exposure on immune function. Elevated IL-10 and PGE2 levels, however, cannot explain all of the effects due to JP-8 exposure (e.g., decreased organ weights and decreased viable immune cells), as treatment with a PGE2 inhibitor did not completely reverse the immunosuppressive effects of jet fuel exposure. Thus, low concentration JP-8 jet fuel exposures have significant effects on the immune system, which can be partially explained by the secretion of immunosuppressive modulators, which are cumulative over time.     

孕期苯乙基异硫氰酸盐染毒对大鼠子代神经行为发育的影响

目的研究大鼠孕期暴露于苯乙基异硫氰酸盐(PEITC)对子一代(F1)神经发育、早期行为及学习记忆能力等的影响。方法受孕大鼠于孕7～16天分别经口给予0、15、60和120mg/kg PEITC后,观察F1代断崖回避、平面翻正、前肢悬挂、听觉惊愕和嗅觉定位等早期行为发育指标的变化,并应用Y迷宫评价仔鼠学习记忆能力,对F1代大鼠大脑海马区神经元发育情况进行病理学检查。结果孕大鼠60和120mg/kg染毒剂量组,其F1代仔鼠平面翻正、断崖回避以及嗅觉定向等早期行为指标发育延迟,且运动学习能力下降;120mg/kg染毒剂量组F1代仔鼠海马区平均神经元密度为142±6.7,与阴性对照组相比有显著差异(P<0.05),且神经元损伤评分增至0～1级。结论大鼠孕期给予PEITC,可对F1代大鼠早期行为和学习记忆产生抑制和干扰;PEITC在15mg/kg剂量条件下无神经发育毒性和行为致畸作用。     

Benzene and naphthalene in air and breath as indicators of exposure to jet fuel

Aims: To estimate exposures to benzene and naphthalene among military personnel working with jet fuel (JP-8) and to determine whether naphthalene might serve as a surrogate for JP-8 in studies of health effects.

Methods: Benzene and naphthalene were measured in air and breath of 326 personnel in the US Air Force, who had been assigned a priori into low, moderate, and high exposure categories for JP-8.

Results: Median air concentrations for persons in the low, moderate, and high exposure categories were 3.1, 7.4, and 252 µg benzene/m³ air, 4.6, 9.0, and 11.4 µg benzene/m³ breath, 1.9, 10.3, and 485 µg naphthalene/m³ air, and 0.73, 0.93, and 1.83 µg naphthalene/m³ breath, respectively. In the moderate and high exposure categories, 5% and 15% of the benzene air concentrations, respectively, were above the 2002 threshold limit value (TLV) of 1.6 mg/m³. Multiple regression analyses of air and breath levels revealed prominent background sources of benzene exposure, including cigarette smoke. However, naphthalene exposure was not unduly influenced by sources other than JP-8. Among heavily exposed workers, dermal contact with JP-8 contributed to air and breath concentrations along with several physical and environmental factors.

Conclusions: Personnel having regular contact with JP-8 are occasionally exposed to benzene at levels above the current TLV. Among heavily exposed workers, uptake of JP-8 components occurs via both inhalation and dermal contact. Naphthalene in air and breath can serve as useful measures of exposure to JP-8 and uptake of fuel components in the body.

     

宫内铅暴露对大鼠神经行为发育的影响

目的研究低水平宫内铅暴露对Wistar大鼠早期行为及学习记忆等神经行为发育的影响。方法雌性大鼠分别经0．5，1．0和2．0mmol／LPbCl2暴露后，观察其F1代仔鼠断崖回避、平面翻正、前肢悬挂、空中翻正、听觉惊愕和视觉定位等早期行为发育以及应用水迷宫、Y迷宫检测仔鼠学习记忆能力。结果孕鼠经2．0mmol／LPbCl2染毒后，其仔鼠听觉惊愕和视觉定位等行为指标的发育出现了延迟；而1．0和2．0mmol／LPbCl2染毒后的孕鼠，导致其仔鼠的空中翻正发育延迟，仔鼠的空间方位辨别学习能力和运动学习能力、短时记忆和长时记忆能力的损害。结论宫内低水平铅暴露具有较强的行为发育毒性。     

Identification of target genes responsive to JP-8 exposure in the rat central nervous system

Concern for the health risk associated with occupational exposure to jet fuel has emerged in the Department of Defense. Jet propulsion fuel-8 (JP-8) is the fuel used in most US and North Atlantic Treaty Organization (NATO) jet aircraft, and will be the predominant fuel both for military land vehicles and aircraft into the twenty-first century. JP-8 exhibits reduced volatility and lower benzene content as compared to JP-4, the predominant military aircraft fuel before 1992, possibly suggesting greater occupational exposure safety. However, the higher rates of occupational exposure through fueling and maintenance of increasingly larger numbers of aircraft/vehicles raise concerns with respect to toxicity. Clinical studies of workers experiencing long-term exposure to certain jet fuels demonstrated deficits in CNS function, including fatigue, neurobehavioral changes, psychiatric disorders, and abnormal electroencephalogram (EEG). In the present study, cDNA nylon arrays (Atlas Rat 1.2 Array, Clontech Laboratories, Palo Alto, CA) were utilized to measure changes in gene expression in whole brain tissue of rats exposed repeatedly to JP-8, under conditions that simulated possible real-world occupational exposure (6 h/day for 91 days) to JP-8 vapor at 1,000 mg/m3. Gene expression analysis of the exposure group compared to the control group revealed a modulation of several genes, including glutathione S-transferase Yb2 subunit (GST Yb2); cytochrome P450 IIIAl (CYP3A1); glucose-dependent insulinotropic peptide (GIP); alpha1-proteinase inhibitor (alpha1-AT); polyubiquitin; GABA transporter 3 (GAT-3); and plasma membrane Ca2+-transporting ATPase (brain isoform 2) (PMCA2). The implications of these vapor-induced changes in gene expression are discussed.