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Abstracts / Toxicology L

The following results were found in a total of 155 biologicalamples and 199 environmental samples:

Biological samples MEDIA: 5634, SD 4.76, minimum 0.82 and max-imum 29.52.Environmental samples: MEDIA: 0.039, SD 0.022, minimum 0.02and maximum value of 0152.The correlation was positive for a p-value <0.001 and R2 = 0.9572.

We conclude that the application of both procedures is effectiven monitoring BEI workers exposed to mercury.

oi:10.1016/j.toxlet.2010.03.286

104-031nfluence of genetic polymorphism of metabolizing enzymesf polycyclic aromatic hydrocarbons in excretion of-hydroxipirene and cotinine by occupational exposure

. Georgieva 1, T. Panev 1, B. Dragova 2, V. Nikolova 1, D.hohadjieva 1, T. Popov 1, S. Garte 3

National Center of Public Health Protection, Bulgaria, 2 Sofiaedical University, Bulgaria, 3 Genetics Research Institute, Bulgaria

ain sources of polycyclic aromatic hydrocarbons (PAHs) areigarettes smoke, environment, food or occupational exposure. Theata presented in this study is a part of a project for examination ofNA damage resulting from PAHs exposure. The aim of the studyas assess the effect of polymorphisms of metabolizing enzymes

n the biomarkers of exposure to PAHs and cigarettes smoke. Thetudy subjects were 47 traffic policemen, 49 bus drivers and 50 con-rol without professional exposure to PAHs. It was investigated tenolymorphisms of CYP1A1, GSTM1, GSTT1, GSTP, NAT2, EPHX, andYP1B1. 1-Hydroxypyrene in urine was measured as a biomarkerf exposure to PAHs.(benz(a)pyrene). Urinary cotinine, one of theain metabolites of nicotine, has been measured in urine as a

iomarker for assessment of direct or passive exposure to cigarettemoke. Effect of polymorphic variation of enzymes involved in bio-ransformation of PAHs on cotinine and 1-HP was analyzed.

High frequency of carriers of ‘wild’ type in GSTT and CYP1A1n the study subjects in this study demonstrates the need for newtudies and in individuals exposed to other chemical agents.

Results of this research fill the scarce data for Bulgarian popula-ion and demonstrate the need to extend the research of individualusceptibility by exposure to chemical agents from the environ-ent or working environment. The study of the importance of

he variants of enzymes involved in biotransformation of toxicantsffecting individual sensitivity will allow an individual preventionmong exposed and, accordingly—decrease the health risk.

oi:10.1016/j.toxlet.2010.03.287

196S (2010) S37–S351 S77

P104-032Assessment of micronucleus frequencies in lymphocytes ofworkers exposed to fumes of bitumen—Results of the humanbitumen study

P. Welge, B. Marczynski, M. Raulf-Heimsoth, A. Spickenheuer, B.Kendzia, E. Heinze, A. Erkes, M. Hagnia, H.U. Käfferlein, B. Pesch,T. Brüning

Institute for Prevention and Occupational Medicine of the GermanSocial Accident Insurance - Institute of the Ruhr-Universität Bochum(IPA), Germany

The possible genotoxic risk from exposure to fumes of bitumenduring application of hot asphalt is under discussion with respectto the occurrence of small amounts of polycyclic aromatic hydro-carbons. Therefore we investigated the micronucleus frequenciesin peripheral blood lymphocytes of 225 bitumen-exposed workers(age 17–62 years) and 69 non-bitumen exposed road construc-tion workers (age 18–64 years) in Germany using a cross-shiftdesign. Micronuclei (MN) were determined with a standard methodusing cytochalasin B. Regression models were applied with thelog-transformed micronucleus frequency as dependent variable inorder to estimate bitumen effects.

The median of the exposure to fumes of bitumen in the exposedworkers was 3.0 mg/m3. The median micronucleus frequencywas 6.0 MN/1000 binucleated lymphocytes (BNC) (interquartilerange (IQR) 4.0–8.5) in exposed workers and 6.0 MN/1000 BNC(IQR 4.0–8.3) in non-exposed workers before shift. After shift weobserved 6.5 MN/1000 BNC (IQR 4.4–9.3) in exposed workers and6.5 MN/1000 BNC (IQR 4.0–9.0) in non-exposed workers. In a lin-ear regression model age was the most prominent predictor ofthe micronucleus frequencies (exp(beta) = 1.33; 95% CI 1.24–1.43;p < 0.0001 post shift). We observed a weak difference between theexposure groups (p = 0.032) only in the post shift model and noassociation with the concentration of fumes of bitumen. On thebasis of a single shift exposure measurement a relation betweenexposure to fumes of bitumen and micronucleus frequencies couldnot be detected.

The difference between the micronucleus frequencies beforeand after shift was within the biological variability. The age-relatedincrease of micronucleus frequency is in concordance with otherstudies and was found in both exposure groups indicating thatduration of exposure to fumes of bitumen is not the cause. Thedetermined micronucleus frequencies in lymphocytes revealed nomutagenic potential of fumes of bitumen under the exposure cir-cumstances of this study.

doi:10.1016/j.toxlet.2010.03.288

P104-033Hydrofluoric acid HF burn injuries decontamination in ex vivohuman eye and skin models

L. Mathieu 1, E. Lati 2, F. Burgher 1, C. Fosse 1, P. Gasser 2, A. Hall 3,L. Peno-Mazzarino 2, N. Schrage 4

1 Prevor Laboratory, Valmondois, France, 2 BIO EC Laboratory,Longjumeau, France, 3 Colorado School of Public Health, Denver,Colorado, USA, 4 Aachen Centre of Technology Transfer inOphthalmology, Aachen, Germany

Introduction: Hydrofluoric acid (HF) is a partially dissociated acidbut has serious dermal, local and systemic toxicity. The objectiveswere: firstly to present results on HF penetration in the cornea

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developed in Spain. In the group of patients studied, women’s occu-pational poisonings were more related with irritant fumes and theyhad a better prognosis than men’s.

doi:10.1016/j.toxlet.2010.03.291

78 Abstracts / Toxicology L

nd through the skin with ex vivo models; secondly, to compareifferent washing decontamination products.

Methods: Rabbit corneas were exposed to 2.5% HF and pen-tration of the acid was monitored by high-resolution Opticaloherence Tomography. The same method was used to compareashing with Hexafluorine®, a specific active decontamination

olution for HF, to washing with tap water or 1% calcium glu-onate. No decontamination served as the control group. In skinxperiments, human explants were exposed to 70% HF and theenetration through epidermis and dermis was followed by opticalicroscopy of histological samplings. Then, Hexafluorine® wash-

ng versus tap water washing followed by 2.5% calcium gluconateintment were compared to no decontamination (control group).

Results: The rabbit cornea was completely penetrated inminutes with 2.5% HF solution. Water decontamination andalcium gluconate decontamination, delayed the complete pene-ration of the cornea but could not prevent it (opaque cornea). Onlyexafluorine® washing allowed the transparency of the cornea

o be preserved, even 1 h after washing ended. The human skinxplants were completely penetrated within 5 min with 70% HFolution, resulting in epidermal and dermal alterations. Waterecontamination + 2.5% calcium gluconate, delayed and decreasedhese alterations, but did not prevent them. Hexafluorine® decon-amination prevented all cellular alterations in this human skin exivo model.

Conclusion: These experimental burns are reproducible and rep-esentative of HF burn evolution. It is also in accordance with theesults observed for washing of contaminated workers. Water rins-ng + calcium gluconate ointment decreases and delays HF burnvolution, but repeated applications are needed. Hexafluorine®

revents HF burns even with concentrated HF exposure.

oi:10.1016/j.toxlet.2010.03.289

104-034election of biomarkers to investigate the protection effect of-acetylcysteine on 2,5-hexanedione neurotoxicity in ratsxposed to 2,5-hexanedione

.E. Torres 1, L. Gon3̧alves 2, A.P. Dos Santos 1, M.C. Batoréu 1,

.L. Mateus 1

Research Institute for Medicines and Pharmaceutical SciencesiMed.UL), Portugal, 2 Center for Interdisciplinary Research Egasoniz (CiiEM), Portugal

,5-Hexanedione (2,5-HD) is the metabolite responsible by n-exane neurotoxicity due to its reaction with primary lysinemino groups leading to the formation of pyrrolyl adducts in axo-ium neurofilaments proteins. Subsequently, the autoxidation ofyrroles may form pyrrole–pyrrole crosslinking responsible by n-exane neurotoxicity.

However, stable secondary pyrrole adducts with sulphy-ril groups of GSH or cysteine may be formed inhibitingyrrole–pyrrole crosslinking and the formation of these adductsay be a protection mechanism against 2,5-HD neurotoxicity.In this study, we investigated the interference of N-

cetylcysteine (NAC) on 2,5-HD toxicokinetics by measuring thehanges on biomarkers of exposure in urine of rats ip exposed todoses of 2,5-HD (400 mg/kg) and in urine of rats ip co-exposed

o 6 doses of 2,5-HD + NAC (400 mg/kg + 400 mg/kg) using GC/FID

nd colorimetric methods. The characterization of primary and sec-ndary pyrrole adducts was performed using LC/MS/MS.

The interference of NAC on 2,5-HD toxicokinetics was evaluatedy measuring the changes on biomarkers of exposure, namely, free

196S (2010) S37–S351

and total 2,5-HD and pyrrole derivatives in urine of rats exposed to2,5-HD and co-exposed to 2,5-HD and NAC and the results show amarked decrease on excretion of the referred biomarkers.

Standards of N-acetyl-6-(2,5-dimethylpyrrol-1-yl)norleucineand N-acetyl-6-[3-(N-acetylcysteine-S-yl)-2,5-dimethylpyrrol-1-yl]norleucine were synthesized and the identification of primaryand secondary pyrrole adducts in urine of exposed and co-exposedrats was performed. The identification of cysteine conjugates andlysine conjugates was achieved and a correlation between thesebiomarkers, pyrrole derivatives and 2,5-HD levels in urine of ratsco-exposed to 2,5-HD + NAC was established. Thus, the mechanismof interference of NAC on 2,5-HD toxicokinetics may be explainedthrough the preferential affinity of 2,5-HD to sulphydril groupsinhibiting pyrrole–pyrrole cross-linking in neurofilament proteins.

doi:10.1016/j.toxlet.2010.03.290

P104-035Gender analysis in occupational poisonings in Spain

M.E. Rodríguez 1, V. Uroz 1, S. Nogué 2, B. Climent 3, J.Puiguriguer 4, M.S. Dorado 5, S. Mateo 1, Á. Nieto 1, M.J. Anadón 1

1 Universidad Complutense de Madrid, Spain, 2 Hospital Clínico yProvincial, Barcelona, Spain, 3 Hospital General Universitario,Valencia, Spain, 4 Hospital Son Dureta, Mallorca, Spain, 5 Hospital 12de Octubre, Madrid, Spain

Introduction: The wide spread of women in every work area makesnecessary to study their profile of poisonings, in contrast with men,so that specific accurate preventive actions be developed.

Objective: To study the acute occupational poisoning in womenaccording to hospital records in urgency services from Spain.

Materials and methods: Clinical data from 212 occupationalpoisonings have been collected from urgency services from the fol-lowing hospitals and years: 12 de Octubre, Madrid (2004), ClínicoSan Carlos Madrid (2006–2007), General Universitario, Valencia(2004–2007), Son Dureta, Mallorca (2006–2007) and Clínico andProvincial, Barcelona (1999–2007). Cases were grouped by genderand age (under and over 30 years old).

Results: Women supposed the 35% of the poisonings. The meanage of the patients was 35 years in both groups.

In women, the main toxic agents identified were irritant fumesas chlorine gas (46% of the cases; 32% of the patients were from theelder and 14% from the younger subgroup), followed by causticsand industrial products. Respiratory was the main way of access(57%; 39% from the elder subgroup and 16% from the younger one).The clinical prognosis was good in women, as 96% received hospitaldischarge (66% from the elder and 30% from the younger subgroup).

By the other way, in men’s group the main toxic agents werecaustics (32%, mainly from the elder group). Respiratory was alsothe main way of access (35%). Their clinical prognosis was worsethan in women, as only 88% of them received hospital discharge.

Conclusions: To our knowledge this is the first time that gen-der analysis of the epidemiology of occupational poisonings is