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Background: Most studies on air pollution (AP) exposure have focused on adverse health effects of particulate matter (PM). Less well-studied are the actions of volatile organic compounds (VOCs) not retained in PM collections. These studies quantified chemical and biological properties of both PM2.5 and VOCs. Methods: Samples were collected near the Port of Los Angeles (Long Beach, LB), railroads (Commerce, CM), and a pollution-trapping topography-site (San Bernardino, SB). Quantitative assays were conducted: (1) chemical—prooxidant and electrophile content, (2) biological—tumor necrosis factor-α (TNF-α) and heme oxygenase-1 (HO-1) expression (3), VOC modulation of PM effects and (4), activation of the antioxidant response element (ARE) using murine RAW 264.7 macrophages. Results: SB site samples were the most potent in the chemical and biological assays, followed by a CM railroad site. Only PM2.5 exhibited significant proinflammatory responses. VOCs were more potent than PM2.5 in generating anti-inflammatory responses; further, VOC pretreatment reduced PM-associated TNF-α expression. VOCs significantly increased ARE activation compared to their corresponding PM2.5 which remained at background levels. Conclusion: Ambient VOCs are major contributors to adaptive responses that can modulate PM effects, in vitro, and, as such, need to be included in comprehensive assessments of AP. [ABSTRACT FROM AUTHOR]

The potential adverse health effects of PM2.5(particulate matter with an aerodynamic diameter <2.5 μm) and vapor samples from three communities that neighbor railyards, Commerce (CM), Long Beach (LB), and San Bernardino (SB), were assessed by determination of chemical reactivities attributed to the induction of oxidative stress by air pollutants. The assays used were dithiothreitol (DTT)- and dihydrobenzoic acid (DHBA)-based procedures for prooxidant content and a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) assay for electrophiles. Prooxidants and electrophiles have been proposed as the reactive chemical species responsible for the induction of oxidative stress by air pollution mixtures. The PM2.5samples from CM and LB sites showed seasonal differences in reactivities, with higher levels in the winter, whereas the SB sample differences were reversed. The reactivities in the vapor samples were all very similar, except for the summer SB samples, which contained higher levels of both prooxidants and electrophiles. The results suggest that the observed reactivities reflect general geographical differences rather than direct effects of the railyards. Distributional differences in reactivities were also observed, with PM2.5fractions containing most of the prooxidants (74–81%) and the vapor phase most of the electrophiles (82–96%). The high levels of the vapor-phase electrophiles and their potential for adverse biological effects point out the importance of the vapor phase in assessing the potential health effects of ambient air. Implications: PM2.5 and its corresponding vapor phase, containing semivolatile organics, were collected in three communities in the Los Angeles Basin and examined with toxicologically relevant chemical assays. The PM2.5 phase contained most of the prooxidants and the vapor phase contained most of the electrophiles, whose content was highest in summer samples from a receptor site that reflected greater photochemical processing of the air parcel during its transport. As electrophiles initiate both adverse and adaptive responses to foreign substances by biological systems, their presence in the vapor phase emphasizes the importance of this phase in the overall health effects of ambient air. [ABSTRACT FROM AUTHOR]

Ambient air pollutants have been reported to induce oxidative stress based inflammatory responses in humans and experimental animals. However, most of these reports describe the actions of the particulate phase of ambient and exhaust samples. We describe here results of studies investigating the actions of the vapor phase of ambient air samples collected in the midtown area of Los Angeles on human bronchial epithelial BEAS-2B cells using DNA microarray analysis. Among 26 genes whose expression increased fourfold or more, four genes were associated with detoxifying genes regulated by the transcription factor Nrf2. Consistent with these results, the vapor samples activate the Nrf2-ARE pathway, resulting in up-regulation of heme oxygenase-1 (HO-1), glutamate cysteine ligase modifier subunit, and cystine transporter (xCT) mRNA and proteins. No appreciable increases in pro-inflammatory genes were observed. These results suggest that ambient vapor samples activate the Nrf2-ARE pathway but not an inflammatory response. Also, treatment of the vapor samples with glutathione resulted in reduction in the Nrf2 activation and HO-1 induction, suggesting that electrophiles in vapor samples contribute to this Nrf2-dependent antioxidant or adaptive response. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1292-1300, 2014. [ABSTRACT FROM AUTHOR]

Numerous studies have suggested the association of reactive oxygen species (ROS) with adverse health effects derived from exposure to airborne particulate matter (PM) and diesel exhaust particles (DEP). This redox activity has been attributed to both inorganic and organic species present in these particles, but a clear distinction has not been established between the contribution of each. This article describes an application of an analytical procedure, based on the reaction of salicylic acid with hydroxyl radical to form dihydroxybenzoate (DHBA) isomers, to measure transition metal-based redox activity associated with ambient and diesel exhaust particles. In the procedure, ascorbic acid (AA) is used as electron source for reduction of metal ions and oxygen to generate superoxide, which is further reduced to hydroxyl radical in the presence of transition metal ions. Hydroxyl radical reacts with salicylate to generate DHBA isomers, which are measured by high-performance liquid chromatography (HPLC) with electrochemical detector. Both copper (Cu) and iron (Fe) ions generated DHBA isomers in a concentration-dependent manner but at different rates. The procedure was applied to DEP and ambient particles and the results showed Cu ion to be the major contributor to DHBA formation. The procedure provides a quantitative measure of transition metal-based redox activity associated with ambient samples with different physicochemical properties. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The U.S. Environmental Protection Agency funded five academic centers in 1999 to address the uncertainties in exposure, toxicity, and health effects of airborne particulate matter (PM) identified in the "Research Priorities for Airborne Particulate Matter" of the National Research Council (NRC). The centers were structured to promote interdisciplinary approaches to address research priorities of the NRC. In this report, we present selected accomplishments from the first 6 years of the PM Centers, with a focus on the advantages afforded by the interdisciplinary, center-based research approach. The review highlights advances in the area of ultrafine particles and traffic-related health effects as well as cardiovascular and respiratory effects, mechanisms, susceptibility, and PM exposure and characterization issues. DATA SOURCES AND SYNTHESIS: The collective publications of the centers served as the data source. To provide a concise synthesis of overall findings, authors representing each of the five centers identified a limited number of topic areas that serve to illustrate the key accomplishments of the PM Centers program, and a consensus statement was developed. CONCLUSIONS: The PM Centers program has effectively applied interdisciplinary research approaches to advance PM science. [ABSTRACT FROM AUTHOR]

Quinones are reactive organic compounds known to initiate reactions associated with a host of toxicological events. Their presence in different atmospheres has been demonstrated although their sources remain uncertain. As a result of their reactivity and instability during chemical analysis, only a limited number of studies have reported on atmospheric concentrations of quinones in ambient air. Furthermore, besides the limited information on quinones associated with particulate matter, no previous studies have quantified vapor-phase quinones. We report vapor- and particle-phase concentrations of 1,2- and 1,4-naphthoquinones (1,2-NQ, 1,4-NQ), 9,10-phenanthraquinone (9,10-PQ), and 9,10-anthraquinone (9,10-AQ), measured over a 5-year period in Southern California. The results showed that vapor-phase concentrations of the target quinones were in general higher than those in the particle-phase. Vapor-phase concentrations ranged from 80 pg/m3 for the AQ to 1747 pg/m3 for the 1,4-NQ, and the particle-phase concentrations between 13 pg/m3 for the 1,2-NQ and 250 pg/m3 for 9,10-AQ. The target quinones were found to be distributed between vapor- and particle-phase, with the exception of 9,10-PQ found only in the particle-phase. The differences observed in the concentrations among sites and seasons suggest different source contributions; source sites were dominated by primary sources, while downwind locations showed a high contribution from photochemical activity. [ABSTRACT FROM AUTHOR]

Motor vehicle exhaust emissions are known to exacerbate asthma and other respiratory diseases. Several studies have demonstrated significant associations between living near highly trafficked roadways and increased incidence of asthma and increased severity of asthma-related symptoms, medication usage, and physician visits. This study tested the hypotheses that (1) exposure to particulate matter (PM) near a heavily trafficked Los Angeles freeway would enhance inflammatory and allergic responses in ovalbumin (OVA)-sensitized BALB/c mice compared to sensitized, clean air controls, and (2) there would be differences in response at two distances downwind of heavily traveled freeways because of greater toxicity of PM closest to the freeway. An ambient particle concentrator was used to expose ovalbumin (OVA)-treated BALB/c mice to purified air, to concentrated fine ambient particles, and to concentrated ultrafine airborne particles (CAPs) at 2 distances, 50 m and 150 m, downwind of a roadway that is impacted by emissions from both heavy-duty diesel and light duty gasoline vehicles. Tissues and biological fluids from the mice were analyzed after exposures for 5 days/wk in 2 consecutive weeks. The biomarkers of allergic or inflammatory responses that were assessed included cytokines released by Type 2 T-helper cells (interleukin [IL]-5 and IL-13), OVA-specific immunoglobulin E (IgE), OVA-specific immunoglobulin G1 (IgG1), and pulmonary infiltration of polymorphonuclear leukocytes and eosinophils. IL-5 and IgG1 were significantly increased in mice exposed to CAPs 50 m downwind of the road, compared to responses in mice exposed to purified air, providing evidence of allergic response. No significant increases in allergy-related responses were observed in mice exposed to CAPs 150 m downwind of the road. The biological responses at the 50-m site were significantly associated with organic and elemental carbon components of fine and ultrafine particles (p ≤ .05). The primary source of these contaminants at the roadway sites was motor vehicle emissions, suggesting that particulate matter from motor vehicle fuel combustion could exert adjuvant effects and promote the development of allergic airway diseases. [ABSTRACT FROM AUTHOR]

Ambient concentrations of 15 vapor-and particle-phase (PM2. 5) polycyclic aromatic hydrocarbons (PAHs), listed by the US EPA as priority pollutants, were measured between July 2002 and November 2003 in six Southern California communities participating in a multi-year chronic respiratory health study of schoolchildren. The communities were geographically distributed over two hundred kilometers, extending from Long Beach in coastal Los Angeles, to high mountain areas to the north and west of the Los Angeles basin, and south into Eastern San Diego County. Seasonal and spatial variation in the atmospheric concentrations of PAHs is of interest because this class of compounds includes potent mutagens, carcinogens, and species capable of generating reactive oxygen species (ROS) that may lead to oxidative stress. Naphthalene accounted for 95% of the total PAH mass; annual averages ranged from 89 to 142 ng m-3. Benzo[ghi]perylene (BGP) and the pro-carcinogen benzo[a]pyrene (BAP), present almost exclusively in the particle-phase, ranged respectively from 38 to 231 pg m-3 and 75 and 111 pg m-3, with the highest values observed in Long Beach, a community with a high volume of seaport-related activities, and Lancaster, a commuter dormitory community. A considerable increase in the particle-phase PAH concentration, relative to the vapor-phase, was observed as ambient temperature decreased. Cold/hot season ratios for PAHs in PM2. 5 averaged 5. 7, reaching 54 at Long Beach. The presented data underscore the importance of seasonal variations on atmospheric PAH concentrations. These observations are relevant to future interpretation and analysis of community-scale human health effects research. [ABSTRACT FROM AUTHOR]

Background: Although the mechanisms of airborne particulate matter (PM) related health effects remain incompletely understood, one emerging hypothesis is that these adverse effects derive from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within affected cells. Typically, ROS are formed in cells through the reduction of oxygen by biological reducing agents, with the catalytic assistance of electron transfer enzymes and redox active chemical species such as redox active organic chemicals and metals. The purpose of this study was to relate the electron transfer ability, or redox activity, of the PM samples to their content in polycyclic aromatic hydrocarbons and various inorganic species. The redox activity of the samples has been shown to correlate with the induction of the stress protein, hemeoxygenase-1. Results: Size-fractionated (i.e. < 0.15; < 2.5 and 2.5 - 10 μm in diameter) ambient PM samples were collected from four different locations in the period from June 2003 to July 2005, and were chemically analyzed for elemental and organic carbon, ions, elements and trace metals and polycyclic aromatic hydrocarbons. The redox activity of the samples was evaluated by means of the dithiothreitol activity assay and was related to their chemical speciation by means of correlation analysis. Our analysis indicated a higher redox activity on a per PM mass basis for ultrafine (< 0.15 μm) particles compared to those of larger sizes. The PM redox activity was highly correlated with the organic carbon (OC) content of PM as well as the mass fractions of species such as polycyclic aromatic hydrocarbons (PAH), and selected metals. Conclusion: The results of this work demonstrate the utility of the dithiothreitol assay for quantitatively assessing the redox potential of airborne particulate matter from a wide range of sources. Studies to characterize the redox activity of PM from various sources throughout the Los Angeles basin are currently underway. [ABSTRACT FROM AUTHOR]

Spray painters are potentially exposed to aerosols containing hexavalent chromium [Cr(VI)] via inhalation of chromate-based paint sprays. Evaluating the particle size distribution of a paint spray aerosol, and the variables that may affect this distribution, is necessary to determine the site and degree of respiratory deposition and the damage that may result from inhaled Cr(VI)-containing paint particles. This study examined the effect of spray gun atomization pressure, aerosol generation source and aerosol aging on the size distribution of chromate-based paint overspray aerosols generated in a bench-scale paint spray booth. The study also determined the effect of particle bounce inside a Marple personal cascade impactor on measured size distributions of paint spray aerosols. Marple personal cascade impactors with a modified inlet were used for sample collection. The data indicated that paint particle bounce did not occur inside the cascade impactors sufficiently to affect size distribution when using uncoated stainless steel or PVC substrate sampling media. A decrease in paint aerosol mass median aerodynamic diameter (MMAD) from 8.2 to 7.0 μm was observed as gun atomization pressure increased from 6 to 10 psi. Overspray aerosols were sampled at two locations in the spray booth. A downstream sampling position simulated the exposure of a worker standing between the painted surface and exhaust, a situation encountered in booths with multiple workers. The measured mean MMAD was 7.2 μm. The distance between the painted surface and sampler was varied to sample oversprays of varying ages between 2.8 and 7.7 s. Age was not a significant factor for determining MMAD. Overspray was sampled at a 90° position to simulate a worker standing in front of the surface being painted with air flowing to the worker''s side, a common situation in field applications. The resulting overspray MMAD averaged 5.9 μm. Direct-spray aerosols were sampled at ages from 5.3 to 11.7 s. Overspray and direct-spray results indicated that most of the change in aerosol size distribution occurred between the time the paint aerosol impacted the painted surface and the time the overspray became 2.8 s old. The overall mean MMAD of overspray in the study was 6.4 μm and may have been underestimated due to sampling efficiency biases. If inhaled by a worker, the overspray aerosols evaluated in this study would mostly deposit in the head airways region of the respiratory tract. Paint overspray aerosols contained Cr primarily in the Cr(VI) state. [ABSTRACT FROM AUTHOR]

Spray painters are potentially exposed to aerosol containing Cr(VI) via inhalation of chromate-based paint spray. Two field studies were conducted at an aerospace facility to determine the size distribution and speciation of Cr(VI) in paint spray aerosol. Sampled paint products consisted of sparingly soluble strontium chromate in an epoxy resin matrix, a matrix generally known for its durability and toughness. Personal aerosol samples were collected using Sierra Marple personal cascade impactors and analyzed for Cr(VI) and total Cr. The size distribution of total Cr particles in the paint aerosol had a Mass Median Aerodynamic Diameter (MMAD) of 7.5 μm [Geometric Standard Deviation (GSD = 2.7 μm)] in both field studies. The MMAD of Cr(VI) particles was 8.5 μm (GSD = 2.2 μm). Particles >2 μm constituted 90% or more of the total Cr and the Cr(VI) mass, in all sampled paint aerosols and were lognormally distributed. The target site for respiratory deposition of Cr in the aerosol was estimated based on the mass distribution of Cr according to particle size. On an average, 62% of the Cr and Cr(VI) mass in the paint aerosol consisted of particles >10 μm. This study showed that 71.8% of Cr(VI) mass in paint spray aerosol potentially inhaled by a spray painter may deposit in the head airways region. Only 2.0 and 1.4% of Cr(VI) mass in the paint aerosol may potentially deposit in the alveolar and tracheobronchial region, respectively.The ratio of Cr(VI) mass to total Cr mass was determined in bulk paint and the data indicate that Cr was predominantly in the Cr(VI) valence state, before spraying. The ratio of Cr(VI) mass to total Cr mass was also determined in paint aerosol samples. The data indicated that there was a reduction of Cr(VI) regardless of Cr aerosol particle size. Cr(VI) reduction occurred most likely during the 8 h sample collection time period. These findings are in agreement with the findings that observed Cr(VI) reduction during collection of airborne Cr(VI) in samples of chromic acid mist. The use of Cr(VI) stabilizing sampling media and the storage of samples at lower temperatures (4°C ) during and after sampling may avoid the underestimation of Cr(VI). [ABSTRACT FROM AUTHOR]

Fifteen priority polycyclic aromatic hydrocarbons (PAHs) were measured in two rural communities (Atascadero and Lompoc) located several hundred km northwest of Los Angeles and in four urban communities 40-100 km downwind of Los Angeles (San Dimas, Upland, Mira Loma, and Riverside), during all seasons, from May 2001 to July 2002. PM 2.5 and vapor-phase PAHs were collected, on prebaked quartz fiber filters and PUF-XAD-4 resin, respectively, at 113 LPM, during 24 h periods, every eighth day, and quantified by HPLC-Fluorescence. At all sites vapor-phase PAHs contained >99.9% of the total PAH mass and were dominated by naphthalene (NAP), which varied from about 60 ng m -3 in Lompoc, a community with light traffic, to ∼580 ng m -3 in Riverside, a community traversed by ∼200,000 vehicles day -1 . During summer pollution episodes in urban sites, NAP concentrations reached 7-30 times annual averages. Except for summer episodes, concentrations of low MW PAHs showed small seasonal variations (∼2 times higher in winter). Similar concentrations of particle-phase PAHs were observed at all sites except for Lompoc. Benzo[ ghi ]perylene (BGP), a marker of gasoline exhaust emissions, showed the highest concentration among particle-phase PAHs, varying from 23.3 pg m -3 in Lompoc to 193 pg m -3 in Mira Loma. Benzo[ a ]pyrene and indeno[ 1,2,3-cd ]pyrene, found exclusively in the particle phase, were much higher in urban sites (∼40-100 pg m -3 ), than in Lompoc (∼12 pg m -3 ). Winter particle-phase PAHs were 2 to 14 times higher than summer levels. Particle-phase PAHs were negatively correlated with mean air temperature in urban sites (r = -0.50 to -0.75), probably resulting from surface inversions occurring during winter. The data suggest that in Southern California vehicular exhaust emissions are a major contributor to particle-phase PAHs. [ABSTRACT FROM AUTHOR]

Quinones are reactive organic compounds and are known to initiate reactions associated with many toxicological events. Their presence in air pollution has been demonstrated, but routine quantitative measurements are lacking. A quantitative method for the determination of four quinones was developed using diesel exhaust particles (DEP) and National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 1649a. The method was then used to analyze ambient air samples from different sites in Southern California. After extraction in dichloromethane, the target compounds were converted to their stable diacetyl derivatives and determined by electron impact GC-MS using selected ion monitoring. Calibration plots were obtained with deuterium-labeled internal standards. The four quinones, 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), 9,10-phenanthraquinone (9,10-PQ), and 9,10-anthraquinone (9,10-AQ), were quantified in DEP, in SRM 1649a, and in ambient air samples of PM 2.5 collected in several rural and urban sampling locations upwind and downwind of major emission sources in Central Los Angeles. Mean concentration of individual target quinones ranged from 7.9-40.4 μg/g in the DEP, and from 5-730 pg/m 3 in the PM 2.5 samples. Precision (repeatability and reproducibility) varied from 2-22%. Further measurements of these species in future air samples should be considered in light of their potential health significance. [ABSTRACT FROM AUTHOR]

Co-exposure to methyl ethyl ketone (MEK) potentiates the neurotoxicity of n-hexane in humans as well as in animals. This effect is associated with increased persistence of 2,5-hexanedione (2,5-HD) in blood, probably due to inhibition of 2,5-HD phase II biotransformation by MEK. There is no previous quantitative toxicokinetic model to describe this interaction. In this study we constructed a toxicokinetic model to depict the inhibition of 2,5-HD metabolism and elimination by MEK. Experimental data on 2,5-HD blood concentrations in rats from a published study were used to estimate model parameters. Three different inhibition mechanisms were evaluated: competitive, uncompetitive, and noncompetitive inhibition. Extrapolation from high to low doses was made to assess the interactive effects of MEK on 2,5-HD beyond experimental conditions. The models developed successfully described the toxicokinetic behavior of 2,5-HD when inhibited by MEK. The competitive inhibition model yielded a much lower estimate for the constant (65.5 mg/l) of 2,5-HD inhibition by MEK than did the uncompetitive and noncompetitive models (403 and 440 mg/l, respectively). The apparent half-life of 2,5-HD appeared to be a linear function of the Michaelis-Menten constant, and 2,5-HD and MEK concentrations in rats. The area under the curve of 2,5-HD in blood of rats was a nonlinear function of 2,5-HD and MEK concentrations in the blood. This study highlights the importance of the interactive effect of MEK on deactivation and elimination of 2,5-HD, and further illustrates the advantage of toxicokinetic modeling to investigate chemical interactions associated with exposure to multiple chemical agents. [ABSTRACT FROM AUTHOR]

It has been estimated that 4 of 1,000 live births and 35% of spontaneous abortions are aneuploid and that an important proportion of embryo and newborn aneuploidy is of paternal origin. Exposure to organophosphorous pesticides (OP) has been associated with sperm hyperploidy/polyploidy. Therefore, we aimed to assess the frequency of sperm aneuploidy (X, Y, and 18) and its relationship with urinary OP metabolites in agricultural workers. We performed multicolor fluorescence in situ hybridization on samples from nine men obtained before and during the pesticide spraying season to assess sperm aneuploidy. We measured urinary OP metabolite levels by gasliquid chromatography. Aneuploidies were found in 0.67% of total sperm nuclei. The most frequent aneuploidy was the lack of a sexual chromosome or sex null (0.19%), followed by XY18 (0.15%) and XY18-18 (0.06%). OP metabolites detected at higher concentrations were dimethylthiophosphate, dimethyldithiophosphate, and diethylphosphate (DEP). There were no differences in average aneuploidy frequency or urinary metabolite levels between samples collected before and after exposure. However, Poisson regression analysis adjusted for age, alcohol intake, and sperm concentration showed significant associations between OP metabolite concentrations and increased frequency of sperm aneuploidies. The association was more evident between DEP and sex null, and the risk increased further during the spraying season. Thus, OP exposure could interfere with sperm chromosome segregation and increase the risk for genetic syndromes, such as Turner's. Further studies are required to assess the prevalence of spontaneous abortions, birth defects, and genetic syndromes in agricultural communities. Key words: organophosphorous pesticides, sex null, sperm aneuploidy, Turner syndrome. Environ Health Perspect 109:1237-1240 (2001). [Online 24 November 2001] http://ehpnet1.niehs.nih.gov/does/2001/109p1237-1240recio/abst ract.html [ABSTRACT FROM AUTHOR]

Abstract: The lack of successful disease surveillance methods has resulted in few reliable estimates of workplace-related disease. Hazard surveillance--the ongoing assessment of chemical use and worker exposure to the chemicals--is presented as a way to supplement occupational disease surveillance. Existing OSHA (Occupational Safety and Health Administration) and NIOSH (National Institute for Occupational Health) data systems are adapted to this function to characterize the distribution and type of hazardous industry in Los Angeles County. A new method is developed for ranking potentially hazardous industries in the county using actual exposure measurements from federal OSHA compliance inspections. The strengths of the different systems are presented along with considerations of industrial employment and types of specific chemical exposures. Applications for information from hazard surveillance are discussed in terms of intervention, monitoring exposure control, planning, research, and as a complement to disease surveillance. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The Effect of Outreach Workers' Services on the Medical Care of a Disadvantaged Population," by Donald K. Freeborn and his colleagues.

The neurotoxic aminonitrile dimethylaminopropionotrile (DMAPN) inhibits the crystalline glycolytic enzymes glyceraldehyde‐3‐phosphate dehydrogenase (CAPDH) and fructose‐6‐phosphate kinase (phosphofructokinase, PFK). Preincubation of CAPDH with the aminonitrile enhances the inhibition, indicating that the inhibition is irreversible. The overall bimolecular rate constant kiwas determined to be 2.42 ± 0.21 M−1 min−1. Dithiothreitol (DTT) partially protected the enzyme from inhibition. PFK is also inhibited by DMAPN, but the inhibition is reversible and noncompetitive with a K1 of 2.79 x 10−2 M. DMAPN does not inhibit lactate dehydrogenase (LDH), nor is GAPDH or PFK inhibited by 3,3'‐iminodipropionitrile (IDPN). [ABSTRACT FROM PUBLISHER]

Cyanide release from neurotoxic aminonitriles was measured following in vitro incubation with both microsomes and liver slices. Investigation of cyanide released as urinary thiocyanate following ip aminonitrile administration to rats was also measured. The yield of cyanide in the in vivo study, as measured by the mole percent of administered dose, was greatest from dimethylaminonitrile (DMAA), followed by trimethylaminopropionitrile (TMAPN), dimethylaminopropionitrile (DMAPN), 3,3'‐iminodipropionitrile (IDPN), dimethylaminobutyronitrile (DMABN), and monomethylaminopropionitrile (MMAPN). Urinary excretion of thiocyanate accounted for 48.9% of the administered DMAA, 11.6% of TMAPN, 8.0% of DMAPN, 6.8% of IDPN, 3.1% of DMABN, and 1.8% of MMAPN. Incubation of aminonitriles and related compounds with microsomes or liver slices from rats yielded measurable quantities of cyanide from all the compounds tested except for DMABN, TMABN, and succiononitrile. Quantitative evaluation of the yield of formaldehyde by demethylation following microsomal incubation was also determined. The signs of acute toxicity in rats after ip administration of KCN were similar only to those in rats administered DMAA. [ABSTRACT FROM PUBLISHER]

The article reflects on the need to develop disease surveillance systems to monitor occupational health in the U.S. The Occupational Safety and Health Administration constructed a standardized reporting scheme to monitor both injuries and illness in a systematic way on a national basis. One example of a surveillance development which concentrates on specific companies is the initiation of corporate-wide mortality registry systems designed to explore mortality excesses which may be work-related. The United Auto Workers system is built on a concept of triage which begins with a statement of a suspected problem.