toxicology by gasoline

miller rellim at MAILHOST.TCS.TULANE.EDU
Tue Feb 2 10:43:08 EST 1999

Felix Revilla <felix at inea.uva.es> wrote:
>I would like to know some web or bibliography about toxicity produced by
>inahalation of gases of engines (gasoline, diesel, etc). Thanks

Environ Health Perspect 1998 Dec;106 Suppl 6:1281-1289
Toxicology of Chemical Mixtures: International Perspective.
Feron VJ, Cassee FR, Groten JP
TNO-Nutrition and Food Research Institute, Toxicology Division, Zeist, The

This paper reviews major activities outside the United States on human
health issues related to chemical mixtures. In Europe an international
study group on combination effects has been formed and has started by
defining synergism and antagonism. Successful research programs in Europe
include the development and application of statistically designed
experiments combined with multivariate data analysis and modeling in in
vitro and in vivo studies on a wide variety of chemicals such as petroleum
hydrocarbons, aldehydes, food contaminants, industrial solvents, and
mycotoxins. Other major activities focus on the development of safety
evaluation strategies for mixtures such as the use of toxic equivalence
factors or alternatives such as the question-and-answer approach,
fractionation followed by recombination of the mixture in combination with
a mixture design, and quantitative structure-activity relationship analysis
combined with lumping analysis and physiologically based
pharmacokinetic/pharmacodynamic modeling for studying complex mixtures. A
scheme for hazard identification and risk assessment of complex mixtures
and a consistent way to generate total volatile organic compound values for
indoor air have also been developed. Examples of other activities are
carcinogenicity studies on complex mixtures (petroleum middle distillates,
foundry fumes, pesticides, heterocyclic amines, diesel exhaust, solid
particles), neurotoxicity studies of mixtures of solvents alone or in
combination with exposure to physical factors, and toxicity studies of
outdoor air pollutants, focusing on particulates. Outside the United
States, toxicologists and regulators clearly have a growing interest in the
toxicology and risk assessment of chemical mixtures.
PMID: 9860882

Mutat Res 1998 Jul 8;415(1-2):13-23
Mutagenic and cytotoxic effects of exhaust particulate matter of biodiesel
compared to fossil diesel fuel.
Bunger J, Krahl J, Franke HU, Munack A, Hallier E
Center of Environmental and Occupational Medicine, University of Gottingen,
Germany. jbuenge at gwdg.de

The mutagenic and cytotoxic effects of diesel engine exhaust (DEE) from a
modern passenger car using rapeseed oil methyl esters (RME, biodiesel) as
fuel were directly compared to DEE of diesel fuel (DF) derived from
petroleum. Combustion particulate matter was collected on glass fiber
filters coated with polytetrafluoroethylene (PTFE) from an exhaust dilution
tunnel using three different engine test cycles on a chassis dynamometer.
Filters were extracted with dichloromethane in a soxhlet apparatus for 12
h. The mutagenicity of the extracts was tested in the Salmonella
typhimurium /mammalian microsome plate-incorporation assay using strains
TA97a, TA98, TA100, and TA102. The toxicity to the established cell line
L929 (mouse lung fibroblasts) was investigated in the neutral red assay. In
the tester strains TA98 and TA100 a significant increase of mutations
resulted for the particle extracts of both fuels, but for DF the revertants
were significantly higher compared to RME. The highest levels of revertants
were observed in tests including a cold start phase. This was probably due
to incomplete combustion in the cold engine and a lower conversion rate of
the cold catalytic converter. Testing with activated liver S9 fraction
induced a slightly lower increase of revertants in most experiments. TA97a
and TA102 showed no significant enhancement of spontaneous mutations. In
the FTP-75 test cycle RME extracts showed slightly higher toxic effects to
the L929 cells than DF, whereas in the other tests no significant
differences were observable. These results indicate a higher mutagenic
potency of DEE of DF compared to RME. This is probably due to the lower
content of polycyclic aromatic compounds (PAC) in RME exhaust, although the
emitted masses of RME were higher in most test procedures applied in this
PMID: 9711258, UI: 98377117

Exp Lung Res 1998 Jan-Feb;24(1):85-100
Diesel exhaust particles induced release of interleukin 6 and 8 by (primed)
human bronchial epithelial cells (BEAS 2B) in vitro.
Steerenberg PA, Zonnenberg JA, Dormans JA, Joon PN, Wouters IM, van Bree L,
Scheepers PT, Van Loveren H
Laboratory for Pathology and Immunobiology, National Institute of Public
Health and the Environment, Bilthoven, The Netherlands.
p.steerenberg at rivm.nl

Several epidemiological studies have recently shown associations of
increased premature mortality rates with ambient particulate air pollution.
Diesel exhaust particles (DEP) may constitute an important part of
(ultra)fine particulate air pollution in urban areas and may therefore
contribute to its toxicity. Epithelial lining of the respiratory tract may
be the first target of the toxic effects of DEP, that upon exposure may
release pro-inflammatory mediators such as interleukin 6 and 8 (IL-6,
IL-8), ultimately causing airway tissue damage and immune alterations. In
this study the effects of in vitro DEP exposure (0.04-0.33 mg/mL) on IL-6,
IL-8 production by a human bronchial epithelial cell line (BEAS-2B) were
investigated. For comparison, the production of interleukins during
exposure to silica and titanium oxide (TiO2) were also studied,
representing relatively toxic and non-toxic particles, respectively.
Scanning and transmission electron microscopy showed that the size of the
DEP particles ranged between 25 to 35 nm and that DEP was phagocytized by
BEAS-2B cells. An increase in IL-6 and IL-8 production (11- and 4-fold,
respectively) was found after 24 or 48 h of exposure to DEP compared to the
non-exposed cells. This increase was lower compared to silica (17- and
3.3-fold) and higher as compared to TiO2 which showed no increase for IL-6
and IL-8. To study the DEP effect on inflammation-primed cells, BEAS-2B
cells were exposed to both tumor necrosis factor-alpha (TNF-alpha) and
subsequently to DEP. Exposure to TNF-alpha caused a strong increase in IL-6
and IL-8 production. Additive effects on the IL-6 and IL-8 production by
BEAS-2B cells were found after TNF-alpha priming and subsequently exposure
to DEP, only at a low dose of DEP and TNF-alpha (0.05-0.2 ng/mL). In
conclusion, BEAS-2B phagocytized DEP and produced an increased amount of
IL-6 and IL-8. In TNF-alpha primed BEAS-2B cells, DEP increased interleukin
production only at low concentrations of DEP and TNF-alpha. Whether this
increased production of pro-inflammatory interleukins affects vulnerable
balances in the immune system, such as T help-1 and T help-2 subsets
ratios, resulting in an altered resistance to respiratory tract infections
or altering the expression of respiratory allergy, is the subject of
further studies.
PMID: 9457471, UI: 98118797

Int Arch Allergy Immunol 1997 Oct;114(2):167-74
Diesel exhaust particulates enhance eosinophil adhesion to nasal epithelial
cells and cause degranulation.
Terada N, Maesako K, Hiruma K, Hamano N, Houki G, Konno A, Ikeda T, Sai M
Department of Otorhinolaryngology, Chiba University, School of Medicine,
Chiba City, Japan.

Diesel exhaust particulates (DEP) are a common air pollutant from
diesel-engine-powered car exhaust and are thought to cause chronic airway
diseases. On the other hand, eosinophils are major components of allergic
inflammatory disorders such as asthma, nasal allergy and atopic dermatitis.
We examined the effects of DEP and DEP extract (extract of polyaromatic
hydrocarbons) on eosinophil adhesion, survival rate and degranulation.
Eosinophils, human mucosal microvascular endothelial cells (HMMECs) and
human nasal epithelial cells (HNECs) were preincubated in the presence or
absence of DEP and DEP extract. 35S-labeled eosinophils were allowed to
adhere to monolayers of HMMECs and HNECs. After washing, 35S radioactivity
was determined and numbers of adherent eosinophils were calculated using
each standard curve. The effects of DEP and DEP extract on eosinophil
survival rate and degranulation were also determined. Although neither DEP
nor DEP extract affected the adhesiveness of HMMECs and HNECs to
eosinophils, 5 ng/ml of DEP extract and 50 ng/ml of DEP extract each
significancy increased eosinophil adhesiveness to HNECs (134+/-9 and
143+/-8%, respectively; p<0.01 vs. control), but neither effected
eosinophil adhesiveness to HMMECs. DEP extract also induced eosinophil
degranulation without changing the eosinophil survival rate. Given that
eosinophil-derived lipid mediators and toxic proteins play important roles
in the development of nasal allergy, the above findings strongly suggest
that DEP plays an important role in promoting the nasal hypersensitivity
induced by enhanced eosinophil infiltration of epithelium and eosinophil
PMID: 9338611, UI: 97478316

MMWR Morb Mortal Wkly Rep 1996 Nov 29;45(47):1029-32
Deaths from motor-vehicle-related unintentional carbon
monoxide poisoning--Colorado, 1996, New Mexico,
1980-1995, and United States, 1979-1992.

Carbon monoxide (CO) is a colorless, odorless, toxic gas that is a product
of incomplete combustion. Motor vehicles, heaters, and appliances that use
carbon-based fuels are the main sources of this poison. Most fatal
unintentional CO poisonings associated with motor vehicles are preventable
and can result from differing mechanisms of exposure; 1) operation of a
motor vehicle with a damaged or malfunctioning exhaust system and an
inadequately ventilated passenger compartment, 2) operation of a motor
vehicle in an enclosed space (e.g., a garage) with inadequate ventilation,
and 3) use of auxiliary fuel-burning heaters inside a passenger compartment
or in a camper. This report describes the investigation of deaths
associated with multiple motor-vehicle-related CO poisonings in Colorado on
November 3, 1996, summarizes a review of such deaths in New Mexico during
1980-1995, and presents geographic and seasonal patterns in national death
rates for 1979-1992. These findings indicate that deaths from
motor-vehicle-related unintentional CO poisonings increase during winter
months and that death rates from CO poisoning in stationary motor vehicles
are highest in states with colder average winter temperatures.
PMID: 8965803, UI: 97113563

Toxicol Lett 1996 Nov;88(1-3):233-6
Screening of the gasoline lead load in school children in the Czech Republic.
Pelech L, Malina L, Cikrt M, Janousek S
National Institute of Public Health, Prague, Czech Republic.

The determination of erythrocyte zinc protoporphyrin (ZZP) was implemented
as an indirect method for assessing lead levels in the blood in the
follow-up of Czech children regarding the lead load due to automobile
traffic. Simultaneously, basic indicators of the red blood picture were
studied. A screening study was conducted with 2668 school-age children
residing permanently in three different regions of our country. The
differences in basic hematological indicators, i.e. number of erythrocytes,
hemoglobin content, hematocrit and red blood cell volume, like the
differences in zinc protoporphyrin in the peripheral blood, did not confirm
the initial hypothesis on the relatively greater load of the Czech child
population due to lead from exhaust fumes of combustion motors. Also, no
regional differences were observed. The differences found in the
abovementioned indicators reflect the influence of an overall environmental
pollution rather than that of a toxic effect of lead.
PMID: 8920742, UI: 97079010

Am J Med 1995 Feb;98(2):145-55
Warehouse workers' headache: emergency evaluation and management of 30
patients with carbon monoxide poisoning.
Ely EW, Moorehead B, Haponik EF
Section on Pulmonary and Critical Care Medicine, Bowman Gray School of
Medicine, Winston-Salem, North Carolina 27157-1054.

BACKGROUND: Carbon monoxide (CO) is the leading cause of fatal toxic
inhalation in the United States, but the medical literature contains few
reports of mass exposures. Warehouse workers' headache (WWH) is an
infrequently reported form of CO poisoning due to industrial exposure.
METHODS: We describe 30 persons who developed WWH after inhaling exhaust
from a propane-fueled forklift, their emergency medical management at a
small community hospital, and their long-term courses. RESULTS: Workers
with more direct exposures to vented exhaust had significantly higher
expired CO levels (21.1 +/- 0.7% versus 8.4 +/- 4.8%, P< 0.0001) and higher
acute symptom scores (9.0 +/- 2.2 versus 4.7 +/- 3.3, P = 0.01) than
persons with less direct exposures. Work location, expired CO levels, and
acute symptom scores did not correlate with symptom scores 2 years after
exposure. Workers experiencing acute difficulty concentrating or confusion
had higher expired CO levels than persons with neither of these symptoms
(16.3 +/- 6.7% versus 8.4 +/- 5.2%, P = 0.005) and developed higher chronic
symptom scores (3.9 +/- 3.0 versus 1.1 +/- 1.5, P = 0.04), suggesting that
this subgroup may require closer follow-up for long-term complications.
CONCLUSION: With earlier recognition of ongoing CO toxicity, this disaster
would likely have been averted. Since CO exposures are more common than is
often recognized, general internists must be familiar with the
manifestations of CO toxicity, its timely evaluation, management, and
PMID: 7847431, UI: 95150087

Biochem Soc Symp 1995;61:153-61
Biological and biochemical effects of air pollutants: synergistic effects
of sulphite.
Hippeli S, Elstner EF
Lehrstuhl fur Phytopathologie, Labor fur angewandte Biochemie, Technische
Universitat Munchen, Weihenstephan, Germany.

Air pollution has become a major public and political concern since the
beginning of industrialization, particularly motor exhaust over the past
three decades. Epidemiological studies, together with clinical trials and
experiments in exposition chambers (including biochemical model reactions),
have contributed to our knowledge of potential dangers and increased our
understanding of the corresponding mechanisms and dose-response effects.
Comparison of the threatening reports that appear almost daily in the press
with the digest of over 800 scientific publications allows the statement
that the impact of ozone and nitric oxide on the health and performance of
plants and animals is widely overestimated and appears to be used as a
political instrument. In contrast, the combination of SO2 with soot and
asbestos particles may represent an underestimated toxic potential. In this
communication, we shall concentrate on basic redox mechanisms involving SO2
and important target molecules, as well as looking at the cooperative
effects of sulphite and soot particles.
PMID: 8660392, UI: 96232731

Am Ind Hyg Assoc J 1991 Dec;52(12):542-6
Contaminant reduction by ventilation in a confined space model--toxic
concentrations versus oxygen deficiency.
Garrison RP, Lee KY, Park C
School of Public Health, University of Michigan, Ann Arbor 48109.

Airborne contaminants can create hazardous conditions in confined spaces
(CS) across a broad range of concentrations, e.g., from relatively low,
potentially toxic levels (ppm) to much higher levels (%) causing oxygen
deficiency. This study investigated ventilation characteristics for
isobutylene (IBE) at relatively low concentrations, simulating toxic
levels. Experimental data were compared to results from previous studies of
oxygen deficiency. Data were obtained at several locations in a cubical CS
model, with several variable test parameters: ventilation mode (exhaust and
supply), volume flow rate ("air changes" per hour), and ventilation
inlet/outlet elevation (% of model height). Findings indicated similar
ventilation characteristics, in general, for simulated toxic (IBE) levels
compared to oxygen deficiency. Both IBE and O2 deficiency data have shown
that supply ventilation is typically more effective than exhaust and that
CS locations aligned with supply outlets experience much more rapid
contaminant reduction than do other locations. The data suggest that highly
accurate predictions of ventilation characteristics cannot be expected for
all cases with widely different contaminants and concentrations. Findings
from this study indicate that ventilation guidelines for one range of
contaminant concentration (e.g., causing oxygen deficiency) can be extended
reasonably to encompass a broader range of concentration (e.g., to include
toxic or flammable atmospheres).
PMID: 1781433, UI: 92143038

Z Gesamte Hyg 1991 Jan;37(1):29-31
Assessment of diagnostic lung function and diagnostic laboratory parameters
in workers exposed to diesel exhaust below ground in comparison with
non-exposed workers. [Article in German]
Krause M, Kummer G, Friedrich K, Bergert K, Selbmann K
Gesunchertswesen Wismut, Arbeitshygienisches, Zentrum.

Toxic gases caused by the use of large Diesel-driven devices in underground
mines may lead to impairment of health, especially in the respiratory
system. By means of occupational hygiene supervision it may be checked if
the effectiveness of accomplished occupational hygiene measures are
sufficient. By an enlarged examination programme of the respiratory
function and laboratory diagnostic investigation miners exposed to
Diesel-exhaust-gas were compared within the above mentioned supervision
with a non-exposed population. In this study was not found any difference
between the respiratory results attributed to influence of
Diesel-exhaust-gas. Among the laboratory parameters the exposition to
Diesel-exhaust-gas will only affect the mercapturic acid, however, which
also may be influenced by other factors. Under the conditions of the
measured low degree of exposition was not found any correlation between the
level of mercapturic acids and the duration of exposure as well as to the
actual degree of exhaust-gas exposition.
PMID: 1709316, UI: 91228464

Am J Ind Med 1989;15(5):545-56
Minnesota Highway Maintenance Worker Study: cancer mortality.
Bender AP, Parker DL, Johnson RA, Scharber WK, Williams AN, Marbury MC,
Mandel JS
Minnesota Department of Health, Minneapolis 55440.

Highway maintenance workers (HMWs) have been exposed to a broad range of
potentially toxic substances, including diesel fuels and exhaust, asphalts
and tars, herbicides, gasoline, polynuclear aromatic hydrocarbons, benzene,
and lead. The number of current and former state, county, and municipal
HMWs in the United States exceeds 500,000, yet the health risks of this
occupation had never been studied. To fill this void and to respond to the
public perception that Minnesota HMWs were at high risk of developing
leukemia, an occupational cohort mortality study was conducted of Minnesota
HMWs employed between 1945 and 1984. Leukemia mortality in HMWs with 30-39
years of work (standardized mortality ratio [SMR] = 425; 95% confidence
interval [CI] = 171-876) and urologic cancer mortality in HMWs with 40-49
year latency (SMR = 292; CI = 117-602) were significantly elevated. The
extent to which these and other findings were directly related to work
exposures is unknown. Further investigations to resolve the significance of
the risks associated with the HMW occupation are currently underway.
PMID: 2741960, UI: 89300813

Am J Ind Med 1986;10(2):177-89
Lung cancer and diesel exhaust: a review.
Steenland K

The evidence from animal studies indicates that organic extracts of diesel
particulate are mutagenic and carcinogenic. Of four animal inhalation
studies, two have been positive and two have been largely negative. The
most recent data indicate that inhalation studies may be positive only with
high doses of exhaust. Human studies of diesel-exposed occupations have
been inconclusive. These studies have focused on truck drivers, bus drivers
and garage workers, railroad workers, and heavy equipment operators. Most
human studies have not been able to estimate exposure to diesel exhaust.
Negative studies have frequently suffered from insufficient potential
latency. Positive studies have often failed to control for smoking, and
have sometimes involved confounding occupational exposures. In general, the
occupational epidemiology of diesel-exposed workers is made difficult by
the fact that many of the suspected toxic components of diesel-exhaust are
also present in cigarette smoke and in ambient air. There are two ongoing
epidemiologic studies in the United States, focusing on railway workers and
truck drivers, which attempt to overcome prior difficulties. Preliminary
data from the study of truck drivers indicates an excess of lung cancer
among workers in the trucking industry compared to the U.S. population, but
these data need to be controlled for smoking and analyzed according to
diesel exposure.
PMID: 2428240, UI: 86320278

J Appl Toxicol 1985 Oct;5(5):301-5
Pulmonary function responses in cats following long-term exposure to diesel
Moorman WJ, Clark JC, Pepelko WE, Mattox J

Long-term inhalation studies were carried out to evaluate the toxic
pulmonary effects of diesel engine emissions. Cats were exposed for over 2
years to whole, diluted diesel exhaust at levels expected to produce frank
toxic effects. During the first 61 weeks of exposure, the cats received
exhaust having a particulate level of 6 mg m-3. This was followed by a
doubling of the exposure level from weeks 62 to 124 resulting in
particulate levels of 12 mg m-3. No definitive pattern of pulmonary
function response was observed following 61 weeks; however, a classic
pattern of restrictive lung disease was found at 124 weeks. The
significantly reduced lung volumes and diffusing capacity were indicative
of a pulmonary interstitial response which was later verified by
PMID: 2414357, UI: 86035147

Dr. Charles A. Miller III,   rellim at mailhost.tcs.tulane.edu
Dept. Environmental Health Sciences, SL29
Tulane-Xavier Center for Bioenvironmental Research and
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Ave.
New Orleans, LA 70112
(504)585-6942, fax (504)584-1726
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