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Abstracts / Toxicology L

he area, which became later the largest open air cassiterite miningite of the world, expressing a considerable economic importanceor Rondônia and Brazil. Since the 1970s the area received manyeople from all over the country looking for an opportunity of earn-

ng money from the mining activity. The mining waste was used,ntil the beginning of this decade, to pave the streets and the areashere people build their houses. The aim of this study is to calcu-

ate the dose of manganese which the community is exposed to. Thexposure assessment mainly focused on soils exposure and inges-ion of vegetables in areas covered with waste materials. In order tovaluate the distribution of the metals (cadmium, chromium, man-anese, nickel and copper) in the region, samples were collected inhe mining area, as well as in residential and remote areas, whichre not under direct influence from the mining activity. Geographicnformation system techniques were used in the study in order toetermine the spatial distribution of the exposure. The populationas divided in ages of 6 months until 4 years old, from 4 to 8 years

ld, from 8 to 14 years old and those older than 15. The programsed to calculate the doses was Crystal Ball. The results showedhat manganese concentrations in soils ranged from 20.25 mg/kgo 2706.96 mg/kg (±581.17) and the exposure doses ranged from.16 to 3.18 mg/kg/day, depending on the age. The high exposuref determinate groups can be explained by the local conditions tohich the population is submitted.

oi:10.1016/j.toxlet.2010.03.254

103-045he compatible solute ectoine prevents neutrophilic lungnflammation induced by environmental model nanoparticlesn vivo

. Unfried 1, U. Sydlik 1, H. Peuschel 1, C. Albrecht 1, A. Bilstein 2, J.rutmann 1

Institut für umweltmedizinische Forschung (IUF),Germany, 2 BitopG, Witten, Germany

ackground: Inflammatory airway reactions induced by environ-ental air pollution contribute to several human diseases including

OPD, asthma, and cardiovascular diseases. We recently reportedhat inflammatory reactions of the lung induced by this exoge-ous stress may be prevented by the application of compatibleolutes (Sydlik U. et al., AJRCCM 2009, 180: 29–35). The currenttudy describes the influence of ectoine on inflammatory kineticss well as the molecular mechanisms responsible for the preventiveffect.

Methods: Inflammatory kinetics were investigated in ratsreated with carbon nanoparticles alone or together with the com-atible solute ectoine. The inflammatory response was determinedeveral time points after particle application. The molecular mech-nisms of the preventive strategy were investigated in cultured ratnd human lung epithelial cells.

Results: Nanoparticle-induced neutrophilic airway inflamma-ion in the presence of ectoine was significantly reduced up to68 h after nanoparticle application. This effect proved to be dose-ependent (0.01–1 mM) and specific for compatible solutes, sinceontrol substances showed no effect. Analyses of the underlyingode of action revealed that ectoine acted on lung epithelial cells

y preventing pro-inflammatory signaling pathways by particles initro and in vivo.

Conclusion: The data clearly demonstrate a robust sustainednti-inflammatory effect of ectoine on nanoparticle-induced neu-rophilic lung inflammation in vivo. As compatible solutes areompliant natural products without known toxic potential, we pro-

196S (2010) S37–S351 S67

pose that this group of substances may be used for the preventionof particle-induced airway inflammation in humans.

doi:10.1016/j.toxlet.2010.03.255

P104Occupational Toxicology

P104-001Modulation of phase-II enzymes activities by ovariectomy inliver and kidney of benzene treated rats

Y. Verma.

C.C.S. University, India

Benzene is an occupational hazard and environmental toxicant andrequires metabolism to induce its toxic effects. Human studies haveshown that benzene is primarily metabolized by CYP450-2E1. Freeradical formation during the peroxidatic metabolism of benzeneplays a role in benzene-induced toxicity. The potential of oxida-tive stress in benzene toxicity has also been established. We haveshown that progesterone could modulate benzene toxicity. How-ever the effect of progesterone on phase-II enzymes are not known.Therefore a study on the role of progesterone on phase-II enzymesand its modulation by ovariectomy in liver and kidney of benzenetreated rats was undertaken.

This paper describes the results on glutathione-S-transferase(GST), glutathione peroxidase (GPX), catalase in liver and kidney ofrats subjected to benzene treatment after ovariectomy. Potential ofDNA damage by ovariectomy, if any, also been carried out by usingsingle cell gel electrophoresis. Our results evince that progesteronedecreased the GST activity in liver and kidney. Further ovariectomydecreased the GST activity. Progesterone hormone suppressed thehepatic GPX activity. Hepatic catalase was found diminished inbenzene and progesterone treated rats. Results on DNA damageby using single cell gel electrophoresis also confirmed our obser-vations on phase-II enzymes. These investigations are importantfrom occupational health point of view. It is suggesting that antiox-idant enzymes system of a target organ is controlled by prevailinghormone profile. Nevertheless it could be modulated by suitablehormonal therapy. Epidemiological studies on this aspect need tobe made in future.

doi:10.1016/j.toxlet.2010.03.257

P104-002Cancer risk assessment for refractory ceramic fibres fromAFSSET occupational exposure limit (OEL) committee

M. El Yamani, H. Modelon.

French Agency for Environmental and Occupational Health Safety,France

Refractory ceramic fibres (RCFs) are used in thermal insulationapplications where temperature exceeds 350 ◦C. Asbestos materialswere earlier commonly used for these purposes. RCFs are classifiedas carcinogens class 2 by the IARC.

AFSSET-OEL committee has reviewed data characterizing RCFsand information about potential health effects obtained fromexperimental and epidemiologic studies.

In chronic animal inhalation studies, exposure to RCFs producedan increased incidence of mesotheliomas in hamsters and lung

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ancer in rats. Studies of worker populations with occupationalxposure to airborne RCFs have shown an association betweenxposure and the formation of pleural plaques, increased preva-ence of respiratory symptoms, decreases in pulmonary function,nd irritation.

AFSSET-OEL committee considered that the carcinogenic poten-ial of RCFs is linked to a genotoxic mechanism with no threshold

ode of action. A model assuming a linear relationship betweenose and the response (lung cancer) have been used to establishhe occupational exposure limit.

Using the approach of benchmark dose modelling such asescribed by Maxim et al. (2003) which produced RCF unit potencyalues ranging from 1.4 × 10−4 to 7.2 × 10−4, the model retained byFSSET-OEL committee indicated that an excess cancer risk of 10−4

s associated with a concentration of 0.02 respirable f/cm3 based on0 years of occupational exposure. The linear modelling approach

n this analysis of the exposure–response relationship using the ani-al data takes into consideration possible differences in dosimetry

nd lung burden between rats and humans.

oi:10.1016/j.toxlet.2010.03.258

104-003ose-dependent neurologic abnormalities in workers exposed

o 1-bromopropane

. Ichihara 1, W. Li 2, E. Shibata 3, Z. Zhou 2, S. Ichihara 4, H.ang 1, Q. Wang 2, J. Li 2, L. Zhang 1, Y. Takeuchi 5, X. Ding 6

Nagoya University Graduate School of Medicine, Japan, 2 Fudanniversity School of Public Health, China, 3 Aichi Medical University,

apan, 4 Mie University, Japan, 5 Nagoya University, Japan, 6 Shanghainstitute of Planned Parenthood Research, China

bjectives: 1-Bromopropane (1-BP) is a neurotoxic compound innimal and human, but its dose-dependency in human remainslusive. The present study investigated the health effects of 1-BPnd its dose-dependency in workers.

Methods: Data of 60 female and 26 male workers in three 1-BPactories in China and the same number of age-, sex- and region-

atched controls were analyzed. Workers were interviewed andxamined with a battery of neurobehavioral tests, nerve conduc-ion velocity tests in lower limbs, vibration sense, hematologicalnd biochemical tests. The time-weighed average (TWA) exposureevels of individual workers were estimated with passive samplers.he exposed workers were divided by the median value of the indi-idual exposure level into two groups of equal number for analysisf variance (ANOVA) followed by regression analysis on exposureevel.

Results: Regression analysis on exposure level following ANOVAhowed dose-dependent increase in distal latency of tibial nervend threshold for vibration sense in both toes in female work-rs. The analysis also showed dose-dependent decrease in scoresf tension and fatigue of profile of mood status (POMS) in femaleorkers. Blood urea nitrogen (BUN), aspartate aminotransferase,

actate dehydrogenase and follicle stimulating hormone increasedose-dependently in female workers and BUN increased dose-ependently in male workers. Red blood cell (RBC) and hematocrithowed dose-dependent decrease in female workers. Amongarameters showing significant dose-dependency, DL, vibrationense in both toes, Fatigue of POMS and RBC showed significant

ifference from the control in low-exposure group (median ofxposure level: 2.21 ppm) as well as high-exposure group (medianf exposure level: 18.31 ppm) in female workers.

196S (2010) S37–S351

Conclusions: The results suggest that exposure to 1-BP inducesdose-dependent neurotoxicity and possible hemato- and hepato-toxicities in female workers. The study suggests that the lowestadverse effect level is 2.21 ppm.

doi:10.1016/j.toxlet.2010.03.259

P104-004Risk assessment in occupational exposure to formaldehyde:Differences between anatomy and pathology laboratories andformaldehyde-resins production

S. Viegas, C. Ladeira, C. Nunes, J. Malta-Vacas, M. Gomes, M. Brito,J. Prista

ESTeSL, Portugal

Formaldehyde (CH2O), the most simple and reactive of all alde-hydes, is colorless, and readily polymerizing gas at normaltemperature. The most extensive use is in production of resins andhas an important application as a disinfectant and preservative, rea-son why relevant workplace exposure may also occur in pathologyand anatomy laboratories and in mortuaries.

A study was carried out in Portugal, in a formaldehyde produc-tion resins factory and in 10 pathology and anatomy laboratories.It was applied a risk assessment methodology based on Queens-land University proposal that permitted to perform risk assessmentfor each activity developed in a work station. This methodologywas applied in 83 different activities developed in the laboratoriesand in 18 activities of the factory. Also, Micronucleus Test was per-formed in lymphocytes from 30 factory workers and 50 laboratoriesworkers.

In the factory, 94.5% of the activities were classify with low riskand 5.5% with high risk. In the laboratories, 1.41% of the activitieswere classified with very high risk, 36.32% with high risk, 15.49%with medium risk and, finally 46.48% with low risk. These resultswere confirm with the results of the Micronucleus Test perform inboth groups that showed micronucleus mean in lymphocytes wassignificantly higher in the workers from the laboratories (p < 0.05).

Results obtained suggest that preventive and protective mea-sures must be applied particularly in anatomy and pathologylaboratories in order to reduce occupational exposure to this chem-ical agent and, subsequently to prevent adverse effects on workershealth.

doi:10.1016/j.toxlet.2010.03.260

P104-005Occupational exposure to formaldehyde in anatomy andpathology laboratories: Differences between exposure groups?

S. Viegas, C. Ladeira, C. Nunes, M. Gomes, M. Brito, J. Prista

ESTeSL, Portugal

Formaldehyde, also known as formalin, formal and methyl alde-hydes, is a colorless, flammable, strong-smelling gas. It has animportant application in embalming tissues and that result inexposures for workers in the pathology anatomy laboratories andmortuaries.

To perform exposure assessment is necessary define exposuregroups and in this occupational setting the technicians and pathol-ogists are the most important groups. In the case of formaldehyde,it seems that health effects are more related with peak exposuresthan with exposure duration.