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Diesel Fume Notes

Diesel Fume



*          Retrospective cohort study of 55,395 railroad workers followed from 1959 to 1976 resulted in an unadjusted RR for luca = 1.58ss for workers aged 40-44 in 1959 who experienced the longest exposure to diesel exhaust and when adjusted for smoking the RR = 1.44ss; concluded that even after adjusting for smoking history, there still exists an elevated risk of lung cancer in jobs with exposure to diesel exhaust(CTX-29502); see Crump criticism of this study(CTX-29549)
*          Case-control study of US Railroad workers who died between March 1, 1981 and Feb 28, 1982 with diesel exposure assigned based on an IH survey and smoking histories were considered: diesel exhaust exposed jobs with 20+yrs of exposure resulted in an odds ratio OR=1.41ss for lung cancer; concludes assn between particulate matter from diesel exhaust and lung cancer(CTX-29697)
*          Retrospective cohort study of 55407 railroad workers aged 40-64 in 1959 who had started working 10-20yrs earlier; 1694 lung cancer deaths identified; RR = 1.45ss for lung cancer in the group of workers 40-44yo in 1959 - see above, not duplicate publication(CTX-22190)
*          Cohort of 2519 male railway workers with at least 10yrs of service prior to 1967; SMR for overall cohort was 87(healthy worker effect) with SMR for diesel exposed vs controls = 1.42ns; for low diesel exposure group OR = 1.5 and for high exposure group OR = 2.77 compared to unexsposed workers; small increased risk of lung cancer in workers exposed to diesel fumes (CTX-29737)
*          Cohort study of 43,826 male pensioners of the Canadian National Railway Company and cause of death of 17,838 ascertained for those dying between 1965 and 1977.  Main finding was elevated risk of luca for those exposed to diesel fumes with a highly significant dose-response relationship observed(CTX-29752)
*          Pilot study of Railroad Workers showing odds ratio for respiratory cancer in the low exposure group of 1.5 vs 2.77 in the high exposure group, the authors concluding that the results are consistent with an association between diesel fume exposure and lung cancer (CTX-29800).
*          Case-referent study of occupational exposure to diesel fumes shows that in the highest exposure group the RR = 1.63ss(CTX-29420)
*          Case-referent study of 50 lung cancer cases and 154 matched referents, all dock workers exposed to diesel fumes; OR for medium and high exposure groups were low: 1.0, medium OR = 1.6, high OR = 2.8(note dose-response) when smoking and diesel fumes are considered together the medium OR = 2.7 and the high OR = 6.8; nonsmoking category: OR = 1.6 for medium and 2.9 for high dose group; for smokers OR = 10.7 for medium and 28.9 for high dose group; the results indicate that there is an independent effect of diesel exhaust inhalation and a strong interaction with smoking(CTX-29653)

*          Case-control study of lung cancer risk in Germany found that those exposed regularly to diesel exhaust showed an elevated risk of lung cancer after adjusting for smoking(OR = 1.43ss)(CTX-29524)
*          Pooled analysis of case-control studies in Germany based on 3498 confirmed cases of lung cancer and 3541 male population controls; eval of lung cancer risk from all jobs involving exposure to diesel motor emissions: OR = 1.43ss; in heavy equipment operators OR = 2.31ss; tractor drives with over 30yrs experience OR = 6.81ss; for diesel engine locomotive drivers, switchmen, forklift operators OR = 1.53ss(CTX-29541, 29817)
*          RR for lung cancer in Swedish men increased with exposure level; for low, medium and high exposure levels the RRs were 0.95(ns), 1.1(ss), 1.3(ss) respectively and most cancers were SCCs of the lung; concludes that risk of luca increases with increased exposure to diesel fumes in men(CTX-29454)
*          Case-control study in Sweden involving 20 cases of luca with 6 referents for each case; lung cancer risk increased with increasing cumulative exposure to diesel exhaust(D/R); comparing the most highly exposed group with the low exposed group the RR = 2.4ss(CTX-29674).
*          Case-referent study of 50 cases of luca and 154 referents from 15 ports in Sweden studying dock workers showed increase risk of luca as a result of exposure to diesel fumes but no confounding effects of cigarette smoking.  (CTX-29653)
*          Mortality study of Swiss chauffers exposed to diesel fumes show mortality ratio for lung cancer = 2.27ss(CTX-29847)
*          Case-control study of Teamster Union truck drives showed OR = 1.55ns for all drivers and 1.89ss for diesel truck drivers leading to the conclusion that diesel truck drivers have an increased risk of lung cancer(CTX-29676)
*          Case-control study of 2584 cases and 5099 hospital controls showed a crude odds ratio of 1.31ss for risk of lung cancer and diesel fume exposure but when this was corrected for smoking and other confounders the OR was reduced to 0.95ns; when 477 truck drivers were considered versus 946 controls, the crude OR was 1.45ns and was reduced to 1.21ns when corrected for confounders including smoking(CTX-17179,29687dupl)
*          A population-based case-referent study showed increased risk of lung cancer, particularly, SCCs associated with diesel fume inhalation(CTX-29689)
*          Cohort study of potash miners exposed to diesel fumes showed RR = 2.2ns with smoking not being a confounding factor(CTX-29540)
*          NIOSH study of truck drivers, bus drivers, shipyard workers and railroad workers exposed to diesel fumes and concludes that “all analyses resulted in significant positive trends in lung cancer risk with increasing cumulative exposure(CTX-29574)
*          Meta analysis of 47 relevant studies(30 used) and, when adjustments for confounding variables including smoking are made, the adjusted RR = 1.47ss; concludes etiologic role of DE in lung cancer induction(CTX-29547)
*          Meta analysis of 21 studies meeting inclusion criteria; pooled effects showed RR = 1.33ss for luca from occupational exposure to diesel exhaust; sub analysis of case-control showed RR = 1.33ss vs cohort RR = 1.33ss; studies that controlled from smoking RR = 1.35ss vs 1.33ss for those that did not; cohort using internal controls RR = 1.43ss; a positive dose-response was evident; concludes causal link between increased risk of luca and diesel exhaust(CTX-29597).

*          Review of 35 relevant studies show increased risk of luca in truck drivers(RR = 1.17ss), bus drivers(RR = 1.33ss), exposure index in job matrix RR = 1.13ss with positive dose-response shown in 10 of the 12 studies; summary for high diesel exposure RR = 1.44ss(CTX-29491)
*          Review identifies diesel fumes as cause of bronchogenic carcinoma(CTX-29453)
*          Polish review indicates a 30-40% increased risk of lung cancer in those exposed for >20 years to diesel exhausts(CTX-29514)
*          Comparison of inhalation of diesel exhaust particulate extract and cigarette smoke extract using mutagenicity screening assay shows 1 cigarette = 1 year exposure to diesel exhaust at ambient levels(lots of problems with these calcs)(CTX-29548)
*          Risk of LuCa relative to DEP (CTX-29616, 29658); CalEPA concluded that on the basis of a Railroad cohort study of 56,000 workers over 22yrs that “a reasonable and likely explanation for the increased cancer rates in numerous epidemiological studies is a causal association between diesel exhaust exposure and lung cancer”(CTX-29476)
*          Questions causal link between LuCa and DEP (CTX-29617)
*          A critical review of epi studies concludes statistical but not causal evidence exists that long term exposure to diesel fumes, >20yrs, can increase the risk of luca in man(CTX-296290)
*          ACS 2yr mortality study of 461,981 males age 40-79 with known smoking habits and analyzed relative to diesel fume exposure shows RR = 1.18ns(borderline) for luca in general but railroad workers had higher mortality for lung cancer when compared with other occupations - get details(CTX-29694)
*          Cohort of 694 men followed from 1951 to 1983, bus garage workers - found no increase in cancer deaths or in cardiovascular disease(CTX-29701)
*          Case-control study of 502 male lung cancer cases and 502 controls - no association between lung cancer and diesel fume exposure(CTX-29743)
*          Interim results of a long-term prospective mortality study shows an association between diesel exhaust exposure and incidence of lung cancer; a dose-response effect was noted among non smokers and ex-smokers and a higher risk from diesel; ns effects from railroad workers(CTX-29694)
*          Risk of lung cancer calculated by NIOSH shows at diesel particulate exposure of 1.5mg/m3 the risk was 1.5 to 3 in 100(CTX-29806); risk of luca in miners at the upper range of particulate diesel exposure was about 1.5 to 3 in 100(CTX-29809)
*          NIOSH, after review of human and animal data reccomends that whole diesel exhaust be regarded as a potential occupational carcinogen(CTX-29852)
*          IARC classifies diesel engine exhaust as probably carcinogenic in humans(2A)(CTX-29688)
*          Increased risk of lung cancer in truckers related to diesel fume inhalation(CTX-29662)


*          3-nitrobenzanthrone is a very powerful mutagen found in diesel fumes and it binds covalently to DNA after metabolic activation forming multiple adducts with purine bases including deoxyguanosine and deoxyadenosine)(CTX-29458)
*          DNA adduct formation with PAHs (CTX-29459); DNA adduct formation with 1,6-dinitropyrene dinitro-reduction products(CTX-29470); DNA adducts of 1-nitropyrene and PAHs(CTX-29656)
*          Type II alveolar cells showed 4x level of normal DNA adducts after inhalation of DE for 12 weeks in rats(CTX-29682)

*          F344 rats exposed to diesel fumes for 12 weeks and DNA adducts measured at various locations in the lungs; highest level of total DNA adducts detected in nasal tissue was about 1/4 to 1/5 that in peripheral lung where the tumors are found(CTX-24044)
*          1,6-dinitropyrene, a component of diesel exhaust, is a lung carcinogen in male F344 rats and was found to not only result in the dose related formation of DNA adducts but also in the induction of lymphocyte mutations(CTX-29644)
*          Labeled 1,6-dinitropyrene was used to treat F344 rats in a manner known to produce lung tumors and this treatment was found to increase thioguanine resistant splenic lymphocytes  detectible up to 21 weeks post exposure; labeled 1,6-DNP metabolites were found in both lungs and spleens of treated animals; the authors concluded that 1,6-DNP is metabolically activated by nitroreduction to form DNA adducts in both target tissue and spleen lymphocytes and that a tumorigenic dose results in a sign induction of mutant T lymphocytes(CTX-29655).
*          Aromatic DNA adducts found in workers occupationally exposed to diesel fumes(CTX-29650)
*          Pulmonary DNA adducts found in F344 rats exposed to diesel fumes(CTX-29807)
*          DNA adducts in female Wistar rats exposed to diesel fumes(CTX-030).
*          DNA damage of diesel exhaust particles:in-vitro(CTX-29483)
*          F344 rats exposed to diesel emissions at a conc of 7.1mg/m3 and DNA extracted from the lungs after 31mo of exposure; showed intensity of DNA adducts increased in exposed aninmals(CTX29703)
*          DNA adducts measured in lungs of diesel exhaust exposed rat lungs(CTX-29807)
*          Using nrf2 knockout mice (deficient in detox and antioxidant enzymes) to study DNA adduct formation from diesel fumes: hyperplasia and accumulation of the oxidative DNA adduct 8-hydroxydeoxyguanosine were observed in the bronchial epidermis following diesel fume exposure for four weeks(CTX-29457)
*          The finding of 8-hydroxydeoxyguanosine in lungs of exposed mice suggest oxidative DNA damage as a possible step in the carcinogenesis process related to diesel exhaust(CTX-29614, 29850)
*          DEP-induced lung cancer may result from induction of oxidative DNA damage from oxygen radicals resulting in the formation of 8-hydroxyguanosine(CTX-29614)
*          DEP produced superoxide and hydroxyl radicals in respiratory tract of experimental animals; in mouse lungs 8-hydroxydeoxyguanosine, an oxidative degredation product of DNA, was formed by oxygen free radicals produced by DEP and it is possible that this may be a promutagenic lesions leading to lung tumorogenesis(CTX-29633)
*          DEP is mutagenic and causes increase in 8-hydroxyguanosine, a biomarker for oxidative damage in lung tissue; study in mice(CTX-29528); 8-hydroxyguanosine produced as a result of hydroxyl radical formation via superoxide as a result of treatment of mouse lung microsomes with diesel exhaust particulates(CTX-29543); in F344 female rats, 8-hydroxyguanine was used as a marker for response to reactive oxygen species; after intratracheal diesel exhaust particulates, 8-hydroxyguanine levels were increased indicating the involvement of reactive oxygen species in the carc process in rats(CTX-29544)
*          DNA adducts were found in type II pulmonary cells of rats exposed to DEP(CTX-29682)
*          A study in Fisher 344 rats exposed to diesel fumes showed that expression of oncogenes A-raf and proliferating cell nuclear antigen(PCNA) —RNAs were induced in rat lung suggesting that they may have something to do with pulmonary carcinogenesis in rats(CTX-29515)

*          Pulmonary carcinomas from rats inhaling DE or carbon black were analyzed for mutations that would suggest a differential mechanism of carcinogenicity; inactivation of the p53 pathway may have a role in the development of rat lung neoplasms with SCC component(CTX-29635)
*          DEP reduces superoxide dismutase activity in mice but also in-vitro as studied here. This reduction is probably due to the chemical reaction of superoxide with components like quinones which reduce levels of superoxide(CTX-29640)
*          A study of rats treated intratracheally with DEP extract coated on carbon particles and followed by 6ppm NO2 or 4ppm SO2 showed that NO2 and SO2 act as promoters for tumor induction by DEP extracts(CTX-29546)
*          Tests on human bronchial cell lines show that diesel exhaust particulates increase NF-kapaB DNA binding activity and C-fos proto-oncogene expression, both of which could contribute to the proliferation and chronic inflammatin processes included in the lung after DEP exposure(CTX29818)
*          BaP adsorbed onto diesel particles were studied by bolus inhalation in the dog. It was shown that not only is BaP absorbed into general circulation(through alveolar region) and metabolized in the liver but a fraction of the absorbed particulate releases BaP in the airway epithelium where it is metabolized possibly to proximate carcinogen(CTX-29450, 29478)
*          Diesel exhaust particulates decrease GSH in a dose-dependent manner in vitro and are cytotoxic producing reactive oxygen species(CTX-29480)


*          Rats and hamsters were exposed to diesel fumes for 2 years.  Hamsters showed no significant increase in lung tumors but rats demonstrated a statistically significant increase in the incidence of lung tumors exposed to diesel fume emissions compared to controls; a clear dose-response(D/R) was evident(CTX-7132)
*          Exposure of F344 rats to diesel exhaust produced neoplastic malignant lung tumors; in addition, malignant lymphomas were found in both filtered and unfiltered diesel exhaust exposures(CTX-29717)
*          F344 rats exposed up to 30 months showed focal fibrotic and proliferative lung disease acccompanied by a progressive accumulation of soot in the lung and increased prevalence of lung tumors in the high and middle exposure groups; all lung tumors were of epithelial origin and included adenonmas, adenocarcinomas, squamous cysts and SCCs; the results demonstrate that diesel exhaust is a pulmonary carcinogen in the rat(CTX-23117)     
*          F344 rats treated(it) with DEP extracts and exposed to NO2 and SO2 concludes that the two gases act as tumor promotors for DEP extracts(CTX-29546)
*          F344 rats exposed to either carbon black or diesel exhaust for up to 23 months - found lung tumors in both CB and DE exposed rats with the same incidence; authors conclude that carcinogens adsorbed onto diesel particles may not be important in carcinogenesis(CTX-29637); similar findings in another study in rats, and mice with CB, DE and titanium dioxide(CTX-19812).
*          hamsters, mice and rats were exposed to filtered and unfiltered diesel exhaust at about 4mg/m3 for the unfiltered - long term exposure - hamsters did not show lung tumors and rats did show squamous cell tumors in the lungs; mice were equivocal(CTX-6667)

*          F344 rats chronically exposed to diesel fumes or carbon black showed similar prevalences of malignant and benign lung neoplasms in female rats but DE fumes showed higher incidences in male rats; difference not significant; concludes that organic fraction may not play an important role in the lung carcinogenesis of DE(CTX-29637, 29645)
*          Exposure of rats to various concentrations of unfiltered diesel exhaust resulted in cystic keratinizing epitheliomas ranging from 2.5% to 10.7%; in an intratracheal instillation study of extracted diesel particles, an incidence of 16.7% cystic keratinizing epitheliomas were reported; high incidences of keratinizing SCCs found in rats recieving intratracheal B[a]P. (CTX-29591)
*          Long term inhalation and intra-tracheal study of diesel exhaust and diesel particulates in F344 rats; the particulate component but not the gaseous component provoked inflammatory changes and tumors in the lung and the it particles showed similar results; adenomas and adenocarcinomas wre the main histologic types of tumors which developed from the Type II alveolar cell; the tumor incidence was related to dose; point mutations at the K-ras oncogene were noted in the a sign percentage of tumor cells(CTX-29596)
*          Mouse 24mo carcinogenicity study on whole diesel fume exhaust = no tumors(CTX-29619)
*          Heavy-duty diesel exhaust tar administered to Syrian Golden hamsters 1x/wk for 15wks(it) and maintained for life; no differences in tumor incidence between treated and control animals but there was lung damage in treated hamsters(CTX-29641)
*          Two year exposure of rats both normal and emphysemic showed that the latter were not more susceptible to diesel fumes than normal rats(CTX-29677)
*          Intratracheal instillation of 1-nitropyrene and B[a]P adsorbed onto carbon showed papillomas, adenomas, adenocarcinomas, and SCCs in the lungs of treated hamsters(CTX-29678)
*          Focal metaplasia and dysplasia of the respiratory epithelium seen in hamsters treated with whole diesel exhaust for up to 18 months(CTX-29685)
*          Intra-tracheal instillation of diesel exhaust particles into mice for 12mo looking at adenocarcinomas and b-carotene protection(CTX-29472)
*          A 12mo study in rats showing nuclear atypia, positive p53 staining and increased 8-hydroxy-hydroxyguanosine in exposed lungs; conclude that persistent oxidative stress on DNA induced in early exposure along with inflammation appears to play an important role in carcinogenesis process(CTX-29495)
*          SC tumors found after sc injection of either 1-nitropyrene or 3-nitrofluoanthrene in F344 rats; malignant fibrous histiocytomas mainly found(CTX-23444)
*          Meta analysis o f eight chronic inhalation studies which show diesel fumes to be carcinogenic found no tumors at levels of DEP below lung overload levels(CTX-29542)
*          A 24mo study of diesel exhaust in CD-1 mice did produce some thickened and fibrotic areas in the alveolar walls but no lung cancer(CTX-29619)
*          Lung tumors induced in rats by intratracheal administration of CB, original DE or toluene extracted DE; abstr incomplete(CTX-29849)
*          Cell transformation assay using rat tracheal epithelial cells show positive response with activation of DEP(CTX-29585)


*          Mutagenicity of diesel fume particulates(CTX- 29504, 29627) and extracts(CTX-29660)
*          Mono and dinitropyrenes found to be highly mutagenic in fraction of DEP extracted(CTX-29601)

*          1-nitropyrene and 1,3-, 1,6-, and 1,8-dinitropyrenes were found to be strongly mutagenic in one fraction of DEP(CTX-29601)
*          Nitro-components of DEP found to be mutagenic in Ames test including: 1-nitropyrene, 1,8-dinitropyrene, 2-nitrofluoanthene, 3-nitrofluoanthene(CTX-29493)
*          Major mutagens in diesel exhaust particulates are 1,6-dinitropyrene and 1,8-dinitropyrene accounting for about 43% of the total mutagenic activity of the extracts; 1-nitropyrene or 3-nitropyrene accounted for less than 10% of the mutagenic activity(CTX-23221)
*          1-nitropyrene and 2,7-dinitrofluorenone contributed less than 1.5% of the mutagenic activity of diesel exhaust extract in Salmonella(CTX-29749)
*          In a study comparing coke oven, roofing tar, cigarette smoke and diesel exhaust particulates using in-vitro assays, diesel fume particulates were calculated to be the most potent in inducing carcinogenicity(CTX-21781)
*          diesel fume particulates dispersed in pulmonary surfactant and DEP extracts both demonstrated positive responses in Salmonella and SCEs using V79 cells(CTX-29667)
*          Mutagenicity of diesel fume extract was concentrated in the neutral fraction probably due mostly to nitrated PAHs where as the activity in CSC was mainly in the basic fraction(CTX-21696)
*          Mutagenicity of diesel fume extracts were positive in several mutagenicity assays and were found to be highly potent in Ames’ assay relative to cigarette smoke condensate extracts(CTX-29756)
*          Mutagenicity: in mammalian cell systems diesel particulates and cigarette smoke particulates show similar potencies but in the bacterial mutagenesis assays, diesel exhaust particulates result in disproportionately higher potencies than cigarette smoke particulates(CTX-29756)
*          SCEs induced in human lymphocytes by diesel exhaust extracts with a potency of about 1/5 of that of benzo[a]pyrene(CTX-29757)
*          inhalation of diesel fumes in rats have produced lung tumors; co-carcinogenesis bioassays have shown that diesel fumes enhances the effects of other carcinogens; review(CTX-29702)
*          F344 rats and hamsters exposed to diesel fumes; hamsters = no lung tumors; Rats = lung tumors with dose-response(CTX-7132)
*          Mutagenicity of diesel exhaust soot vs carbon black showed that DE was 3x as mutagenic as carbon blak,c in Salmonella assay(CTX-29637)
*          Treatment of Wistar rats with diesel emissions, carbon black and titanium dioxide for two years: looked at DNA adducts and found nitroaromatic adducts but not PAH adducts in rodent exposed to diesel fumes; more details needed(CTX-0030)
*          In a 52wk study of rats exposed to submicron DEP, exposure to lower concentrations resulted in longer long-term lung burdens(CTX-29683)
*          Clearance study in F344 rats exposed to diesel exhaust fumes showed clearance rate decreased with particularly slower alveolar clearance of particle-laden macrophages and leukocytes(CTX-29739, 29742, 29746)
*          Clearance of 14C labeled diesel fumes in F344 rats and guinea pigs showed retention of diesel particulates in rats up to 330 days with three phase clearance half times of 1d, 6d and 80d; for guinea pigs, very little clearance was observed between 10d and 432d with an early clearance phase(CTX-29750)
*          Clearance of particulate exhaust(0.1-0.2um) from diesel engines in rats showed long term clearance rates(half times) between 87 and 99days; the clearance half time for high levels of exposure was 165d, considerably longer than the lower exposure groups(CTX-22063)

*          Using radioactive tracers, clearance of diesel exhaust fumes from F344 rats studied; clearance half times were 1 day for mucociliary clearance and 62 days for alveolar clearance was found with some deposition in the mediastinal lymph notes after 28 days(CTX-29770)
*          F344 rats exposed to diesel exhaust at soot concentrations of 0, 0.35, 3.5 and 7.0mg/m3 for 6, 12, 18 and 24mo exposures; looked at clearance times using a tracer and found long term clearance times of 79, 81, 264 and 240 days for the control, low, mid, high exposure groups indicated impaired particle clearance at higher exposure levels(CTX-23296)
*          Comparison of deposition pattern in rats shows that 82-85% of retained particulates in the alveolar and alveolar duct lumens whereas in humans, about 57% of retained particulates was in the interstitium of the lung - this may account for differences between luca in rat and man(CTX-29474)
*          Review of mechanistic aspects of luca points to particulate overload as an event which may percipitate tumorigenesis in the rat and it may be related to impairment of macrophage function and cytokine activity(CTX-29646)
*          Lovelace Studies showing that rats retained a greater portion of DEP in the lumens of alveolar ducts and alveoli than monkeys while monkeys retained a greater portion in the interstitium than rats; Rats but not monkeys had sign alveolar epithelial hyperplastic inflammatory and septal fibrotic responses to the retained particles(CTX-29603, 29609)
*          F344 rats exposed to 14C labeled 1-nitropyrene both neat and adsorbed onto DEP; t1/2 of elimination in urine and feces was about 15 to 20 hours and the 14C was widely distributed into tissues; NP coated on diesel particles was present 5 times more than in animals treated only with NP; particle association with NP significantly alters the biological fate of the nitro aromatic compound(CTX-29704)
*          Exposure of cats to diesel fumes for 27 months demonstrated peribronchiolar fibrosis with significant increases in lymphocytes, fibroblasts and interstitial macrophages containing diesel particulates; observations during a 6mo recovery period demonstrated a persistent fibrogenic effect on the proximal acinar region of the lung(CTX-29735)



*          3-nitrobenzanthrone, a powerful mutagen contained in diesel fume particulates(CTX-29458, 29563)
*          PAHs in diesel fumes - get details(CTX-29459)
*          2-nitrofluorene, a known carcinogen and direct mutagen, has been identified in diesel fume particulates(CTX-29769)
*          1,6-dinitropyrene, a potent mutagen and carcinogen found in diesel fumes(CTX-29470)
*          Major mutagens in diesel exhaust particulates are 1,6-dinitropyrene and 1,8-dinitropyrene accounting for about 43% of the total mutagenic activity of the extracts; 1-nitropyrene or 3-nitropyrene accounted for less than 10% of the mutagenic activity(CTX-23221)
*          1-nitropyrene and 2,7-dinitrofluorenone contributed less than 1.5% of the mutagenic activity of diesel exhaust extract in Salmonella(CTX-29749)
*          diesel fuel burned in Volvo truck and measured components - get details(CTX-29471)
*          1-nitropyrene, 1,8-dinitropyrene, 1,3-dinitropyrene, 2-nitrofluoranthene, 3-nitrofluoranthene, 6-nitrochrysene, 7-nitrobenz[a]anthracene, 6-nitrobenzo[a]pyrene from DEP were tested for mutagenicity(CTX-29493).

*          1,6-dinitropyrene is known to be highly mutagenic and carcinogenic and is used here as a possible biomarker for diesel fume exposure by looking at DNA adducts and T-lymphocyte mutations, the latter being more long-lived(CTX-29630)
*          A method validation study looked at fluoanthene, pyrene, benz[a]anthracene, benzo[a]pyrene
benzo[g,h,i]perylene as representative PAHs in diesel exhaust samples(CTX-29518)
*          PCDDs/PCDFs in diesel (0.87ng.g) with I-TEQ of 11pg/g (CTX-29552)
*          PCDDs/PCDFs in diesel: highest conc measured in truck engine exhaust = 9.7pgI-TEQ/dry standard per cubic meter(CTX-29557)
*          Five polycyclic mononitroarenes chosen in diesel fume particulates; the corresponding amines can be cleaved from hemoglobin adducts and used as biomarkers for diesel fume exposure; these include 1-nitropyrene, 2-nitrofluorene, 3-nitrofluoranthene, 9-nitrophenanthrene, and 6-nitrochrysene(CTX-29555)
*          1-nitropyrene and 1,3-, 1,6-, and 1,8-dinitropyrenes were found to be strongly mutagenic in one fraction of DEP(CTX-29601)
*          1-nitropyrene as a biomarker for diesel fume inhalation(CTX-29570, 29642)
*          1-nitropyrene metabolism increased significantly in nasal tissue and isolated perfused rat lung after exposure to high concentrations of diesel particulates(CTX-29732)
*          Diesel fumes contain benzene both in gaseous phase and adsorbed on particulates (CTX-29564)
*          Benzene in diesel fumes; suggests using blood parameters, ie ALA synthesis and heme formation, as biomarkers for exposure to diesel fumes(CTX-29557)
*          Using labeled B[a]P adsorbed onto DEPs and instilled intratracheally into rats resulted in demonstration of bioavailability of B[a]P through measurement of excreted label(CTX-29668)
*          2-nitro-9-flurenone found in diesel exhaust particles and is mutagenic in Salmonella(CTX-29706)
*          Heavy duty diesel fumes were fractionated; neutral fraction found to contain nitroacetoxy pyrenes, 1-nitropyrene, 1,6-dinitropyrene; in the acidic fraction: nitrohydroxypyrenes including 1-nitro-3-hydroxy pyrene(CTX-29730)
*          Characterization of extractable organics from cigarette smoke condensate and diesel exhaust particulates - get details(CTX-29707); composition of diesel exhaust with particular reference to particle bound organics - get details(CTX-29709, 7191, 29729, 29736, 29744)
*          Analysis of diesel exhaust for particulates, gases and particle size(0.23 to 0.26um)(CTX-29740)
*          As part of a skin painting study on C57mice, chrysene, and benzopyrene was identified in diesel fume(CTX-29775)
*          As part of a hamster inhalation study the following components were measured in unfiltered diesel exhaust: carbon monoxide - 17.9ppm, carbon dioxide - 0.67ppm, sulfur dioxide - 4.9ppm, total hydrocarbons - 8.9ppm, nitrogen oxides - 15.9ppm, oxygen - 19.5% and particulates 4.2mg/m3(CTX-29785)
*          1-nitropyrene and 3-nitrofluoanthene both found in diesel exhaust and both carcinogenic by sc injection in F344 rats(CTX-23444); 3-nitrofluanthrene carcinogenic in man and animals(CTX-29799)
*          composition of diesel fumes monitored(get details)(CTX-29797)
*          diesel fumes contain nitrogen oxides, hydrocarbons, aldehydes, ketones, phenols and suflur compounds and submicron particulates(CTX-29600)

*          Diesel engines emit between 30 to 100 times more particles than gasoline engines and more nitrogen oxides.  Diesel exhaust particles contain over 1000 compounds of which about 100 have been identified; Nitroaromatic compounds are considered to be the major contributors to the mutagenicity of diesel exhaust particles - review(CTX-29702)
*          Diesel emissions collected in cyclone sampler and solvent extracts followed by fractionation showed 28 polycyclic aromatic compounds present in the extract and the ability of each to compete for the TCDD receptor was measured; abstr incomplete(CTX-29842)



*          Reactive oxygen species and resulting factors contribute to cell proliferation and remodeling during recovery after diesel exhaust injury(CTX-29444)
*          Cytotoxicity of DEP on cultured cells of guinea pig respiratory tract shows possible dysfunction of respiratory tissues mediated by oxygen radicals(CTX-29626)
*          Active oxygen species demonstrated in mice exposed to DEP intratracheally(CTX-29488)
*          A study in rats demonstrates peroxinitrite formation leading to pulmonary inflammation as a result of exposure to DEP(CTX-29492)
*          Cytotoxicity mechanism of DEP on human pulmonary artery endothelial cells shows that NO and peroxynitrite was involved in endothelial cell damage(CTX-29487)
*          Apoptosis in macrophages induced by DEP(CTX-29507); apoptosis of alveolar macrophages related to reactive oxygen radicals(CTX-29535)


*          Airway inflammation in volunteers with increased sputum neutrophils and myeloperoxidase(CTX-29509); production of inflammatory cytokines in cultured normal human bronchial epithelial cells(CTX-29511); infiltration of inflammatory cells in rats exposed to diesel fumes(CTX-29513);
*          Airway Inflammation(CTX-29512, 29517, 29523, 29525, 29527, 29558, 29559, 29560, 29573, 29582, 29608, 29631, 29632)
*          Short term inhalation of diesel fumes in volunteers showed marked systemic and pulmonary inflammatory response in healthy human volunteers(CTX-29561)


*          IL-6 and IL-8 production increased in response to DEP in a human bronchial epithelial cell line; these changes may be related to ultimate airway tissue damage and immune alterations(CTX-29595)
*          Guinea pigs exposed for up to 2yrs to diesel fumes both with and without particulates showed increased numbers of alveolar holes with the vapor only exposure showing less alveolar destruction than the whole diesel exhaust fumes(CTX-29622)
*          DEP particulates were found to be more toxic with decreasing particle size and they were toxic to type II and Clara cells(CTX-29526)



*          4-week inhalation in rasH2mice which are sensitive to various genotoxic agents caused airway hyperresponsiveness as measured by airway resistance during acetylcholine inhalation(CTX-29446).
*          Diesel fume particulates as adjuvant in immune responses(CTX-29484, 29494, 29506, 29508, 29520, 29529, 29530, 29532, 29569, 29571, 29579, 29580, 29581, 29587, 29592, 29602, 29607, 29611)

*          Asthma developed in 3 railroad workers exposed to diesel fumes(CTX-29657)
*          Airway remodeling in mice related to thickening of basement membrane involving platelet-derived growth factor(PDGF) (CTX-29489)
*          Airway hyperresponsiveness in mice treated with diesel fume particulates(CTX-29536, 29572); bronchial asthma in mice exposed to diesel fume particulates (it); (CTX-29625)
*          Guinea pigs exposed to diesel exhaust promoted nasal hyperreactivity (CTX-29551, 29568, 29628); guinea pig tracheal preparations - hyperresponsiveness(CTX-29593, 29606)
*          Human nasal hyperreactivity related to eosinophils and DEP(CTX-29605)
*          DEP can enhance B-cell differentiation and by initiating and elevating IgE production, may play an important role in the increased incidence of allergic airways disease(CTX-29613); enhanced IgE production in the human airway resulting from exposure to PAHs on DEPs may be an important factor in the increase in airway allergic response in man(CTX-29643)
*          Asthmatic patients studied and found to be more responsive to DEP probably as a consequence of release of specific pro-inflammatory mediators from the bronchial epithelial cells(CTX-29554)
*          Three cases of persistent asthma as a result of inhalation of diesel fumes for long periods; methacholine challenge positive(CTX-29657)
*          Experimental evidence to show that the essential features of asthma such as chronic inflammation with eosinphilic infiltration, mucus hypersecretion and airway hyperresponsiveness has been caused by diesel particles and that the effects may be due to active oxygen species(CTX-29848)



*          Impaired clearance of Listeria following exposure to diesel fumes but not carbon black; concludes effect due to chemical of diesel particles in male SD rats(CTX-29466)
*          DEP suppresses alveolar macrophage cytokine release in response to LPS stimulation reducing the efficiency of the immune system(CTX-29531)
*          DE has adverse effect on antigen-specific IgE antibody production in mice through alteration of the cytokine network(CTX-29612)
*          Mice exposed to diesel exhaust showed an enhanced susceptibility to lethal infection by streptococcal pathogens(CTX-29789)
*          Diesel fumes depressed phagocytosis and affected immunologic processes of the lung against infection in rats and monkeys(CTX-29716)


*          CTX-29473, 29500, 29501,29539, 29588
*          Influences autoimmune disease(CTX-29545)
*          activation of human complement by DEP in alveolus(CTX-29589)
*          Low doses of diesel exhaust is shown to adversely affect the cytokine and antibody production in mice by altering CD4+ and CD8+ T-cell functions(CTX-29447)



*          Acute effects of diesel fumes: eye and nasal irritation, lung function changes, respiratory changes, headache, fatigue, and nausea; Chronic effects: cough, sputum production, lung function decrements; diesel exhaust is one important factor contributing to allergy pandemic and acts as an adjuvant to allergen and thereby increases sensitization response(CTX-29467)

*          Heavy exposure to diesel exhaust has produced lung cancer in rats but the studies in mice are questionable and the studies in hamsters are negative.  Experimental studies of short term exposures in humans show that lung inflammatory and other cellular effects can occur after single exposures and Epi data suggests that heavy occupational exposure to DE probably increases the risk of mortality from both lung cancer and other noncancer pulmonary diseases; the small magnitude of these increases does not allow for quantitative estimates of risk with a high degree of certainty(CTX-296498)
*          Acute effects of diesel fume exposure include odor, eye irritations, lung function decrements, cardiovascular symptoms and some non-specific effecs; Lung function decrements are considered to be chronic effects.  Also, there is an association with lung cancer and possibly bladder cancer; direct effects of particle load may include retardation of lung clearance, inflammation and increased cell proliferation as demonstrated in rodents.The particles may also prolong the residence time of particulate organics or induce generation of reactive oxygen species(CTX-7201)
*          A study of 232 workers in diesel bus garages showed symptoms of cough, itching, burning or watering eyes, difficult or labored breathing, chest tightness and wheeze; prevalence of burning eyes, headaches, difficulty breathing, nausea and wheeze were higher in diesel bus garage workers compared to a control population(CTX-29699)
*          Heavy equipment operators, truck and tractor drivers, bus drivers, taxi drivers, chauffeurs, and motor vehicle drivers are at an increased relative risk of cancers of the trachea, bronchus and lung; diesel exhaust, when inhaled chronically at high concentrations is a pulmonary carcinogen in rats, questionable in mice and non carcinogen in hamsters.(CTX-29810)
*          Review of health effects of inhaling diesel fumes - includes non-cancer effects; ENT irritation and concludes that studies support the conclusion that diesel exhaust is a lung carcinogen in humans(CTX-29815)
*          Review - diesel fumes can exacerbate asthma, can cause bronchitis although this is confounded by smoking; can cause irritation of the respiratory tract; prevalence of pneumoconiosis is low; epi evidence is weak for luca(CTX-29600)


*          Exposure of 12 healthy adults to diesel exhaust both filtered and unfiltered resulted in increased airway resistance Raw and specific airway resistance SRaw was significant; no difference between filtered and unfiltered relative to brochochoconstriction(CTX-29615)



*          possible increased risk of colon cancer, not definitive(CTX-29469)
*          Dose-dependent decrease in daily sperm count in mice expsoed to diesel exhaust(CTX-29538)
*          Dose related follicle-stimulating hormone, luteinizing hormone and testicular hyaluronidase resulting in decreased sperm production in diesel exhaust exposed rats(CTX-29550)
*          Case-Referent study of diesel fume inhalation and prostate cancer reports a OR = 3.7ss for subjects exposed to more than 25 dose-years relative to unexposed(CTX-26998)

*          SMRs for esophageal cancer in those exposed to combustion products including bus garage workers = 289ss with a range from 150 to 386(CTX-21970)
*          SMR = 193 for esophageal cancer in bus garage workers(n=695)(CTX-2197)

*          Based on a case-control study of 235 male patients with laryngeal cancer, no association was found with diesel fume exposure(CTX-29638)
*          Exposure of rats to diesel fumes and filtered diesel fumes showed that both reduced bone resorption(increased bone minerals) in growing rats but that the gaseous contributed more to this effect than the particulates(CTX-29620)
*          Possible relationship between colorectal cancer and inhalation of diesel exhaust(CTX-29689)
*          A study of 283 male diesel bus garage workers showed pulmonary function deficits in workers (CTX-29696)       
*          After 124 week inhalation study in cats, sign reduced lung volumes and diffusion capacity indicative of a pulmonary interstial respons was noted(CTX-29728)
*          Exposure of F344 rats to diesel emissions showed trend toward increased pulmonary arterial wall thickness compared to controls(CTX-29724)
*          Exposure to diesel exhaust was positively associated (ns) with risk of bladder cancer among current and former smokers who has smoked more than 15 cigs per day(CTX-29448)
*          Possible increased risk of bladder cancer in railroad workers exposed to DEP(CTX-29491)
*          Bladder cancer in those exposed to diesel fumes, based on 136 cases and 272 matched controls showed little or no elevated risk when corrected for smoking(CTX-29680)
*          Bladder cancer not elevated in those exposed to diesel fumes based on case-control study involving 194 cases and 582 controls(CTX-29731)
*          study of 136 cases of bladder cancer corrected for confounding variables including smoking shows no support for a causal link to diesel fume exposure(CTX-29680)

*          IH survey of road drivers, local drivers, dock workers and mechanics; looked at sub-micron sized elemental carbon; found geometric mean exposures from 3.8ug/m3 in long distance drivers to 13.8ug/m3 in dock workers(CTX-29664).
*          Exposure of individual railroad workers to diesel exhaust correcting for smoking by measuring urinary nicotine and cotinine and using phenanthrene in collected particulates as marker for diesel fumes(CTX-29673)

*          1-nitropyrene used as biomarker for airborne diesel exhaust in a repair shop for train engines and in the urine of exposed workers; Airborne particulates contained up to 5.6ng/m3 1-nitropyrene and both cumulative and average excretion of urinary metabolites were significantly elevated in diesel mechanics vs office workers(CTX-29649)
*          Nitrogen dioxide used as a marker for diesel fume exposure on 477 railroad workers; findings: signal maintainers: 16-24ppb; clerks/dispatchers/station agents: 23-43ppb; engineers/firers: 26-38ppb; breakers/conductors: 50-74ppb; locomotive shop workers: 95-127ppb(CTX-29684)
*          Study of thirteen job groups in large epi study of railroad workers; looked at particulates in three different ways: total particulates(respirable), adjusted respirable particle concentration(corrected for ETS component), and a third measure which is the extractable mass from the particulates as being representative of diesel exhaust - get details(CTX-21189)
*          Exposure of railroad workers to diesel particulates were measured in various job categories and corrected for ETS.  Respirable particulate matter ranged from 17ug/m3 in clerks to 134ug/m3 in locomotive shop workers(CTX-29692)
*          Exposure of railroad workers to diesel particulates corrected for ETS; the total particulates geometric mean exposure for signal maintainers was 58ug/m3 and 110 for shop machinists and 134ug/m3 for locomotive shop workers(CTX-29692)
*          Mean exposure levels corrected for cigarette smoke was 42ug/m3 for clerks, to 225ug/m3 for hostlers; national means ranged from 33 to 216ug/m3 for the same job groups(CTX-29693)
*          Exposure of firefighters in fire stations for diesel exhaust ranged from 170 to 480ug/m3 TWA(CTX-29698)
*          Measurement of particulate exposure in railroad workers was corrected for environmental tobacco smoke by nicotine analysis showed that repair shop workers and hostelers had the highest exposure to respirable particulates(CTX-21189)
*          Exposure in locomotive repair shops where concentration of respirable particles ranged from 96 to 164ug/m3 with significant mutagenicity being shown for the extracts; concludes that the increased levels of mutagens found in the repair shops is consistent with the excess of lung cancer mortality that has been identified in railroad workers exposed to diesel exhaust(CTX-29811)

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Toxicology Notes and Literature

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