Comparison of internal dose measures of solvents in breath, blood and urine and genotoxic changes in aircraft maintenance personnel

Solvents and fuels are in widespread use both in civilian and military populations. 1,1,1-trichloroethane (TCA), xylene, toluene, methyl ethyl ketone (MEK) and methylene chloride are found in a variety of compounds including degreasing agents, paints, coatings, pesticides and paint strippers. Toluene and xylene are also found in fuels, which are complex mixtures of hundreds of agents. The purpose of this investigation was twofold. The first was to determine the optimum medium to measure internal dose of solvents comparing blood, urine and breath. The second was to determine if low level exposures were associated with genotoxic changes after a short-term exposure of fifteen or thirty weeks. To accomplish the first goal a pilot study was initiated involving eight volunteers who worked in aircraft maintenance including sheet metal, painting and assembly mechanic jobs. Industrial hygiene measurements were evaluated over 30 working days. Breath, blood and a 24-hour urine sample were collected twice to compare internal dose parameters. To achieve the second goal, 58 newly hired subjects were monitored prior to exposure and over 30 weeks to determine if there were genotoxic changes as a result of solvent and/or fuel exposure as measured by sister chromatid exchanges (SCEs) and micronuclei (MN). Exposure groups included workers involved in sheet metal (fuel cell) activities, painting, fueling operations and flight line. Results of the pilot study demonstrated that industrial hygiene air samples and internal breath measures taken on the same day were highly correlated for measuring TCA (r = 0.93) and toluene (r = 0.90) but was not as well correlated for the other compounds. Breath measures were more sensitive for measuring low level exposure than were either analytes in blood or 24-hour urine samples; these latter two measures were usually below the limit of detection. A small but statistically significant increase in the frequency of SCEs occurred after 30 weeks of exposure for sheet metal workers (p = 0.003) and for painters (p = 0.05). The MN frequency in the sheet metal workers initially showed a significant increase by 15 weeks, but by 30 weeks had decreased. Chance occurrence of exposures to other occupational or non-occupational agents can not be eliminated as a cause of the genotoxic results since between 58 and 93 total analytes could be found in the breath of some aircraft maintenance personnel.     

Comparison of Internal Dose Measures of Solvents in Breath,Blood and Urine and Genotoxic Changes in Aircraft Maintenance Personnel

ABSTRACT

Solvents and fuels are in widespread use both in civilian and military populations. 1,1,1-trichloroethane (TCA), xylene, toluene, methyl ethyl ketone (MEK) and methylene chloride are found in a variety of compounds including degreasing agents, paints, coatings, pesticides and paint strippers. Toluene and xylene are also found in fuels, which are complex mixtures of hundreds of agents. The purpose of this investigation was twofold. The first was to determine the optimum medium to measure internal dose of solvents comparing blood, urine and breath. The second was to determine if low level exposures were associated with genotoxic changes after a short-term exposure of fifteen or thirty weeks. To accomplish the first goal a pilot study was initiated involving eight volunteers who worked in aircraft maintenance including sheetmetal, painting and assembly mechanic jobs. Industrial hygiene measurements were evaluated over 30 working days. Breath, blood and a 24-hour urine sample were collected twice to compare internal dose parameters. To achieve the second goal, 58 newly hired subjects were monitored prior to exposure and over 30 weeks to determine if there were genotoxic changes as a result of solvent and/or fuel exposure as measured by sister chromatid exchanges (SCEs) and micronuclei (MN). Exposure groups included workers involved in sheetmetal (fuel cell) activities, painting, fueling operations and flight line.

Results of the pilot study demonstrated that industrial hygiene air samples and internal breath measures taken on the same day were highly correlated for measuring TCA (r=0.93) and toluene (r=0.90) but was not as well correlated for the other compounds. Breath measures were more sensitive for measuring low level exposure than were either analytes in blood or 24-hour urine samples; these latter two measures were usually below the limit of detection. A small but statistically significant increase in the frequency of SCEs occurred after 30 weeks of exposure for sheet metal workers (p=0.003) and for painters (p=0.05). The MN frequency in the sheet metal workers initially showed a significant increase by 15 weeks, but by 30 weeks had decreased. Chance occurrence of exposures to other occupational or non-occupational agents can not be eliminated as a cause of the genotoxic results since between 58 and 93 total analytes could be found in the breath of some aircraft maintenance personnel.     

Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity,reproductive disease and sperm epimutations

Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures.     

Physiologically based pharmacokinetic modeling of the temperature-dependent dermal absorption of chloroform by humans following bath water exposures.

The kinetics of chloroform in the exhaled breath of human volunteers exposed skin-only via bath water (concentrations < 100 ppb) were analyzed using a physiologically based pharmacokinetic (PBPK) model. Significant increases in exhaled chloroform (and thus bioavailability) were observed as exposure temperatures were increased from 30 to 40 degrees C. The blood flows to the skin and effective skin permeability coefficients (Kp) were both varied to reflect the temperature-dependent changes in physiology and exhalation kinetics. At 40 degrees C, no differences were observed between males and females. Therefore, Kps were determined (approximately 0.06 cm/hr) at a skin blood flow rate of 18% of the cardiac output. At 30 and 35 degrees C, males exhaled more chloroform than females, resulting in lower effective Kps calculated for females. At these lower temperatures, the blood flow to the skin was also reduced. Total amounts of chloroform absorbed averaged 41.9 and 43.6 microg for males and 11.5 and 39.9 microg for females exposed at 35 and 40 degrees C, respectively. At 30 degrees C, only 2/5 males and 1/5 females had detectable concentrations of chloroform in their exhaled breath. For perspective, the total intake of chloroform would have ranged from 79-194 microg if the volunteers had consumed 2 liters of water orally at the concentrations used in this study. Thus, the relative contribution of dermal uptake of chloroform to the total body burdens associated with bathing for 30 min and drinking 2 liters of water (ignoring contributions from inhalation exposures) was predicted to range from 1 to 28%, depending on the temperature of the bath.     

ACUTE PULMONARY RESPONSE TO INHALED JP-8 JET FUEL AEROSOL IN MICE

The pulmonary response to JP-8 jet fuel inhalation was investigated by characterizing biomarkers of lung injury, respiratory permeability, pulmonary function, and lung morphology. C57BL/6 and B6.A.D. (Ahrd/Nats) mice, aryl hydrocarbon hydroxylase nonresponsive and slow N -acetylator, were exposed to atmospheres ranging from 0 to 113 mg/m 3 of aerosolized JP-8 jet fuel for 1 h. At 24-30 h after the exposure, pulmonary function testing was performed on anesthetized animals. Respiratory permeability was measured by monitoring the pulmonary clearance of instilled 99 m Tc-labeled diethylenetriamine pentaacetate and then lungs were assigned for bronchoalveolar lavage or histopathology. Bronchoalveolar lavage fluid (BALF) was analyzed for total protein, lactate dehydrogenase (LDH), and N -acetyl--D-glucosaminidase (NAG) as well as cell number and type. Pulmonary responses to JP-8 were similar in both strains of mice. JP-8 exposure between 50 and 113 mg/m 3 caused an increase in respiratory permeability, which was accompanied by BALF increases of total protein, LDH, NAG, and alveolar macrophages. There was also a small increase in BALF neutrophils in the C57BL/6 strain. JP-8 exposures did not have an effect on pulmonary function even though histopathology showed evidence of terminal bronchiole lesions. These results indicate that the acute pulmonary response to permissible exposure levels of aerosolized JP-8 jet fuel can cause changes in respiratory permeability and BALF markers of lung injury. These changes in biochemical, cellular, and pathological parameters following JP-8 exposure provide evidence that occupational exposure to hydrocarbon fuel aerosol is more detrimental than vapor exposure.     

Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation

Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.     

Depletion of Liver Glutathione Levels in Rats: A Potential Confound of Nose-Only Inhalation

Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.     

Use of real-time breath analysis and physiologically based pharmacokinetic modeling to evaluate dermal absorption of aqueous toluene in human volunteers.

Toluene is a ubiquitous chemical that is commonly used for its solvent properties in industry and manufacturing, and is a component of many paint products. Although human exposure to toluene is most likely to be through inhalation, toluene is also found in well and surface water. Therefore, an assessment of the dermal contribution to total toluene uptake is useful for understanding human exposures. To evaluate the significance of these exposures, the dermal absorption of toluene was assessed in human volunteers using a combination of real-time exhaled breath analysis and physiologically based pharmacokinetic (PBPK) modeling. Human volunteers wearing swimsuits were submerged in warm tap water to neck level in a stainless steel hydrotherapy tub containing an initial concentration of approximately 500-microg/l toluene. Volunteers were provided purified breathing air to eliminate inhalation exposures, and exhaled breath was continually analyzed before, during, and post exposure to track the absorption and subsequent elimination of the compound in real time. A PBPK model was used to estimate the dermal permeability coefficient (K(p)) to describe each set of exhaled breath data from 4-6 human volunteers. An average K(p) value of 0.012 +/- 0.007 cm/h was found to provide a good fit to all data sets. Volunteers also participated in a second study phase, in which the subject was allowed to breathe the room air during immersion, thus both dermal and inhalation exposures to toluene occurred. Exhaled breath analyses revealed that concurrent inhalation of volatilized toluene resulted in a transient increase in the peak exhaled-breath level by 100 ppb, or an approximate 50% increase over breath levels observed in dermal-only studies. For perspective, the total intake of toluene associated with oral consumption of 2 liters of water containing toluene at bath water concentrations were estimated to be more than 30 times greater than the dermal contribution due to bathing.     

In vivo exposure of female rats to toxicants may affect oocyte quality

A potential endpoint for female reproductive toxicants is fertilizability of the oocytes. This endpoint has not been adequately examined for mammalian females. The objective of these studies was to evaluate fertilizability of rat oocytes following in vivo exposure to known male reproductive toxicants that exert effects via pathways that do not include endocrine disruption and to 4-vinylcyclohexene diepoxide, known to interfere with early follicular development. Oocytes were obtained from females following exposure and quality assessed by in vitro fertilization rate. One study evaluated fertilizability following 2 weeks exposure of females to inhaled tetrachloroethylene (2h/day, 5 days/week). The remaining studies evaluated fertilizability immediately following 2 weeks exposure via drinking water to tetrachloroethylene, trichloroethylene, the fuel oxidants methyl tertiary butyl ether (MTBE), ethyl tertiary butyl ether (ETBE), tertiary amyl methyl ether (TAME), and a metabolite of the first two ethers 2-methyl-1,2-propanediol (2M2P), and to 4-vinylcyclohexene diepoxide. The percentage of oocytes fertilized was reduced following inhalation exposure to tetrachloroethylene, or consumption of trichloroethylene or TAME. Fertilizability was not altered by exposures to the other reproductive toxicants or to the other fuel oxidants. Consistent with the reduced oocyte fertilizability following exposure to trichloroethylene, oocytes from exposed females had a reduced ability to bind sperm plasma membrane proteins. Female reproductive capability assessed by the endpoint, oocyte fertilizability, was reduced by exposure to trichloroethylene and inhaled tetrachloroethylene.     

Urine and serum biomonitoring of exposure to environmental estrogens I: Bisphenol A in pregnant women

Despite its very low oral bioavailability and rapid elimination, multiple reports of unexpectedly high bisphenol A (BPA) concentrations in the serum of pregnant mothers or cord blood have raised questions about BPA exposures during pregnancy. Thirty healthy pregnant women recruited to the study were evaluated for total BPA exposure over a 30-h period comprising one-half day in the field and one day in a clinical setting. BPA and its metabolites were measured in serum and total BPA was measured in matching urine samples. The mean total exposure was similar to the 50^th percentile of exposure for U.S. women and pregnant women in a large North American cohort. Twenty volunteers had total daily exposures equal to or exceeding the U.S. mean, and six volunteers had exposures exceeding the 75th percentile. Women working as cashiers did not have higher total BPA exposure. BPA was detected in some serum samples (0.25–0.51 ng/ml), but showed no relationship to total BPA in corresponding urine samples, no relationship to total BPA exposure, and had unconjugated BPA fractions of 60–80%, consistent with established criteria for sample contamination. We conclude that typical exposures of North American pregnant women produce internal exposures to BPA in the picomolar range.     

Benzene levels in ambient air and breath of smokers and nonsmokers in urban and pristine environments

Benzene levels in human breath and in ambient air were compared in the urban area of San Francisco (SF) and in a more remote coastal pristine setting of Stinson Beach, Calif. (SB). Benzene analysis was done by gas chromatography-mass spectroscopy (GC-MS). Ambient benzene levels were sevenfold higher in SF (2.6 +/- 1.3 ppb, n = 25) than SB (0.38 +/- 0.39 ppb, n = 21). In SF, benzene in smokers' breath (6.8 +/- 3.0 ppb) was greater than in nonsmokers' breath (2.5 +/- 0.8 ppb) and smokers' ambient air (3.3 +/- 0.8 ppb). In SB the same pattern was observed: benzene in smokers' breath was higher than in nonsmokers' breath and ambient air. Benzene in SF nonsmokers' breath was greater than in SB nonsmokers' breath. Marijuana-only smokers had benzene breath levels between those of smokers and nonsmokers. There was little correlation between benzene in breath and number of cigarettes smoked, or with other benzene exposures such as diet. Of special interest was the finding that benzene in breath of SF nonsmokers (2.5 +/- 0.8 ppb) was greater than that in nonsmokers ambient air (1.4 +/- 0.1 ppb). The same was true in SB, where benzene in nonsmokers breath was greater than ambient air (1.8 +/- 0.2 ppb versus 1.0 +/- 0.1 ppb on d 1 and 1.3 +/- 0.3 ppb versus 0.23 +/- 0.18 ppb on d 2). This suggests an additional source of benzene other than outdoor ambient air.     

The effects of ethylene dibromide on semen quality: A comparison of short-term and chronic exposure

Two occupational field studies were conducted to determine the effects of ethylene dibromide (EDB) exposure on male reproductive potential. The first study was a longitudinal study of 10 EDB-exposed forestry employees and 6 unexposed men conducted in Colorado in the summer of 1983. The exposure time was approximately 6 weeks. The second study was a cross-sectional study of 46 EDB-exposed papaya workers and 43 unexposed men conducted in Hawaii in December 1983 in which the average term of employment was about 5 years. In the longitudinal study, sperm velocity decreased in all 10 exposed men and in only two unexposed men. Semen volume was also decreased in 9 of the 10 exposed men (there was no change in the other man); only two unexposed men had a decrease in their semen volume. The longer term EDB exposure resulted in decreases in sperm motility and viability, suggesting that the short term exposure may slow sperm velocity, but longer exposures cause immotility and cell death. An apparent decrease in semen volume that was observed in the longitudinal study was not statistically significant in the cross sectional study of workers having chronic exposure. However, a significantly higher semen pH was observed in the exposed men compared to the unexposed men in the cross-sectional study. The results from both studies suggest that the accessory sex glands may be affected by EDB exposure.     

Effect of in vivo jet fuel exposure on subsequent in vitro dermal absorption of individual aromatic and aliphatic hydrocarbon fuel constituents

The percutaneous absorption of topically applied jet fuel hydrocarbons (HC) through skin previously exposed to jet fuel has not been investigated, although this exposure scenario is the occupational norm. Pigs were exposed to JP-8 jet fuel-soaked cotton fabrics for 1 and 4 d with repeated daily exposures. Preexposed and unexposed skin was then dermatomed and placed in flow-through in vitro diffusion cells. Five cells with exposed skin and four cells with unexposed skin were dosed with a mixture of 14 different HC consisting of nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, ethyl benzene, o-xylene, trimethyl benzene (TMB), cyclohexyl benzene (CHB), naphthalene, and dimethyl naphthalene (DMN) in water + ethanol (50:50) as diluent. Another five cells containing only JP-8-exposed skin were dosed solely with diluent in order to determine the skin retention of jet fuel HC. The absorption parameters of flux, diffusivity, and permeability were calculated for the studied HC. The data indicated that there was a two-fold and four-fold increase in absorption of specific aromatic HC like ethyl benzene, o-xylene, and TMB through 1- and 4-dJP-8 preexposed skin, respectively. Similarly, dodecane and tridecane were absorbed more in 4-d than 1-dJP-8 preexposed skin experiments. The absorption of naphthalene and DMN was 1.5 times greater than the controls in both 1- and 4-d preexposures. CHB, naphthalene, and DMN had significant persistent skin retention in 4-d preexposures as compared to 1-d exposures that might leave skin capable of further absorption several days postexposure. The possible mechanism of an increase in HC absorption in fuel preexposed skin may be via lipid extraction from the stratum corneum as indicated by Fourier transform infrared (FTIR) spectroscopy. This study suggests that the preexposure of skin to jet fuel enhances the subsequent in vitro percutaneous absorption of HC, so single-dose absorption data for jet fuel HC from naive skin may not be optimal to predict the toxic potential for repeated exposures. For certain compounds, persistent absorption may occur days after the initial exposure.     

A reevaluation of the threshold exposure level of inhaled JP-8 in mice

C57BL/6 mice were nose-only exposed to JP-8 jet fuel at average concentrations of 45, 267, and 406 mg JP-8/m(3) for 1 hr/d for 7 days to further test the hypothesis that exposure to JP-8 concentrations below the current permissible exposure level (PEL) of 350 mg/m(3) will induce lung injury, and to validate a new "in-line, real-time" total hydrocarbon analysis system capable of measuring both JP-8 vapor and aerosol concentrations. Pulmonary function and respiratory permeability tests were performed 24 to 30 hr after the final exposures. No significant effects were observed at 45 or 267 mg/m(3). The only significant effect observed at 406 mg/m(3) was a decrease in inspiratory dynamic lung compliance. Morphological examination and morphometric analysis of distal lung tissue demonstrated that alveolar type II epithelial cells showed limited cellular damage with the notable exception of a significant increase in the volume density of lamellar bodies (vacuoles), which is indicative of increased surfactant production, at 45 and 406 mg/m(3). The terminal bronchial epithelium showed initial signs of cellular damage, but the morphometric analysis did not quantify these changes as significant. The morphometric analysis techniques appear to provide an increased sensitivity for detecting the deleterious effects of JP-8 as compared to the physiological evidence offered by pulmonary function or respiratory permeability tests. These observations suggest that the current 350 mg/m(3) PEL for both JP-8 jet fuel and for other more volatile petroleum distillates should be reevaluated and a lower, more accurate PEL should be established with regard human occupational exposure limits.     

Promotion of noise-induced cochlear injury by toluene and ethylbenzene in the rat.

Ethylbenzene + toluene are known individually to have ototoxic potential at high exposure levels and with prolonged exposure times generally of 4-16 weeks. Both ethylbenzene + toluene are minor constituents of JP-8 jet fuel; this fuel has recently been determined to promote susceptibility to noise-induced hearing loss. Therefore, the current study evaluates the ototoxic potential of combined exposure to ethylbenzene + toluene exposure in a ratio calculated from the average found in three laboratories. Rats received ethylbenzene + toluene by inhalation and half of them were subjected simultaneously to an octave band of noise (OBN) of 93-95 dB. Another group received only the noise exposure which was designed to produce a small, but permanent auditory impairment while an unexposed control group was also included. In two separate experiments, exposures occurred either repeatedly on 5 successive days for 1 week or for 5 days on 2 successive weeks to 4000 mg/m(3) total hydrocarbons for 6 h based upon initial pilot studies. The concentration of toluene was 400 ppm and the concentration of ethylbenzene was 660 ppm. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. Following completion of these tests, the organs of Corti were dissected to permit evaluation of hair cell loss. The uptake and elimination of the solvents was assessed by harvesting key organs at two time points following ethylbenzene + toluene exposure from additional rats not used for auditory testing. Similarly, glutathione (GSH) levels were measured in light of suggestions that oxidative stress might result from solvent-noise exposures. Ethylbenzene + toluene exposure by itself at 4000 mg/m(3) for 6 h did not impair cochlear function or yield a loss of hair cells. However, when combined with a 93-dB OBN exposure combined solvent + noise did yield a loss in auditory function and a clear potentiation of outer hair cell death that exceeded the loss produced by noise alone. No evidence was found for a loss in total GSH in lung, liver, or brain as a consequence of ethylbenzene + toluene exposure.     

Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice

Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (IH) to induce cardiovascular disease, which may be related to oxidative damage. Metallothionein (MT) has been extensively proved to be an endogenous and highly inducible antioxidant protein expressed in the heart. Therefore, we tested the hypotheses that oxidative stress plays a critical role in OSA induced cardiac damage and MT protects the heart from OSA-induced cardiomyopathy. To mimic hypoxia/reoxygenation events that occur in adult OSA patients, mice were exposed to IH for 3 days to 8 weeks. The IH paradigm consisted of alternating cycles of 20.9% O₂/8% O₂ F_IO₂ (30 episodes per hour) with 20 s at the nadir F_IO₂ for 12 h a day during daylight. IH significantly increased the ratio of heart weight to tibia length at 4 weeks with a decrease in cardiac function from 4 to 8 weeks. Cardiac oxidative damage and fibrosis were observed after 4 and 8 weeks of IH exposures. Endogenous MT expression was up-regulated in response to 3-day IH, but significantly decreased at 4 and 8 weeks of IH. In support of MT as a major compensatory component, mice with cardiac overexpression of MT gene and mice with global MT gene deletion were completely resistant, and highly sensitive, respectively, to chronic IH induced cardiac effects. These findings suggest that chronic IH induces cardiomyopathy characterized by oxidative stress-mediated cardiac damage and the antioxidant MT protects the heart from such pathological and functional changes.     

Semen analysis of military personnel associated with military duty assignments

A collaborative study between the U.S. Army Biomedical Research and Development Laboratory (USABRDL) and the National Institute for Occupational Safety and Health (NIOSH) was designed to assess fecundity of male artillery soldiers with potential exposures to airborne lead aerosols. Potential exposure assessment was based upon information provided in an interactive questionnaire. It became apparent from extensive questionnaire data that many soldiers in the initial control population had potentially experienced microwave exposure as radar equipment operators. As a result, a third group of soldiers without potential for lead or microwave exposures, but with similar environmental conditions, was selected as a comparison population. Blood hormone levels and semen analyses were conducted on artillerymen (n = 30), radar equipment operators (n = 20), and the comparison group (n = 31). Analysis of the questionnaire information revealed that concern about fertility problems motivated participation of some soldiers with potential artillery or microwave exposures. Although small study population size and the confounding variable of perceived infertility limit the reliability of the study, several statistically significant findings were identified. Artillerymen who perceived a possible fertility concern demonstrated lower sperm counts/ejaculate (P = 0.067) and lower sperm/mL (P = 0.014) than the comparison group. The group of men with potential microwave exposures demonstrated lower sperm counts/mL (P = 0.009) and sperm/ejaculate (P = 0.027) than the comparison group. Variables used to assess endocrine, accessory sex gland, and sperm cell function were not different than the comparison group. Additional studies, incorporating larger numbers of individuals, should be performed in order to more optimally characterize potential lead and microwave exposure effects on male fecundity.     

Lead-contaminated drinking waters in the public schools of Philadelphia

Lead exposure is a preventable environmental health concern. Young children between the ages of 1 to 6 are most susceptible to its clinical effects. This article reports the results of lead level determinations in the drinking water of Philadelphia's public school buildings and remediation efforts aimed at dealing with this public health concern. METHODS: Water samples were collected from drinking sources in 292 school buildings in Philadelphia from May 2000 through January 2001. These samples were collected and sent to reference laboratories for determination of lead levels. RESULTS: A total of 42.5% (124) of schools had water lead levels not exceeding the action level of 20 ppb, of which 3.1% had nondetectable levels or levels less than 5 ppb. A total of 28.7% of buildings had water lead levels ranging from 20 to 50 ppb, 11.6% had levels between 50-100 ppb, and 17.1% had water lead levels of 100 ppb or more. CONCLUSION: A total of 57.4% of Philadelphia's public school buildings had water lead levels exceeding the Environmental Protection Agencies (EPA) action level of 20 ppb, and 28.7% of school buildings had water with mean lead levels in excess of 50 ppb. Depending on the volume of water consumed, drinking water from school buildings may be a significant source of lead exposure for children in their formative years of development. Although Philadelphia's public school buildings were evaluated, lead-contaminated drinking water in schools is not only an urban concern. School buildings in suburban and rural areas may have similar water lead levels, and testing programs are desirable.     

Neurobehavioural evaluation and kinetics of inhalation of constant or fluctuating toluene concentrations in human volunteers

The health risks of inhalation exposure to volatile organic solvents may not only depend on the total external dose, but also on the pattern of exposure. It has been suggested that exposure to regularly occurring peak concentrations may have a stronger impact on the brain than constant exposure at the same average level. Recent animal experimental studies conducted in our laboratory using relatively high concentrations of toluene have shown different effects on discrimination performance and motor activity during and after exposure, depending on the exposure scenario. Relevance of these findings for man was evaluated in a volunteer study in which 11 healthy men (age 20–49 years) were exposed by inhalation for 4 h to either a constant concentration of 40 ppm toluene or to three 30-min exposure peaks at 110 ppm during this 4 h period. Selected tests from the Neurobehavioural Evaluation System (NES) were performed repeatedly during and after exposure. Blood concentrations of toluene as well as urinary o-cresol excretion were measured at relevant time points.

The results show that toluene concentration in blood increased during constant exposure and fluctuated during occupationally relevant peak exposures. Presumably, brain concentrations showed similar qualitative patterns. No clear changes were observed on neurobehavioural measures of motor performance, attention, perceptual coding and memory, or on measures of mood and affect. The exposure conditions do not seem to induce significant acute changes in central nervous system function similar to those observed at much higher concentrations in animals, although a statistical correlation was found between one motor performance test (Finger Tapping Test with alternating hands) and blood toluene concentrations. Urinary o-cresol excretion appeared to be significantly higher during the first 2 h after exposure.