Medical gloves irritant contact dermatitis risk

Medical gloves irritant contact dermatitis risk

Abstracts / Toxicology Letters 205S (2011) S180–S300 animal studies. In the present study, we investigated modification activity of early-life exposur...

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Abstracts / Toxicology Letters 205S (2011) S180–S300

animal studies. In the present study, we investigated modification activity of early-life exposure to Mn on rat CNS tumoriogenesis induced by transplacental ENU treatment (20 mg/kg b.w., i.v.) on the 17th day of pregnancy. Dams during the lactation period and their offspring after weaning until postnatal week 34 were given diet containing Mn chloride tetrahydrate (MnCl2 ·4H2 O) at 0, 0.002, 0.01 or 0.05%. Intergroup differences in body weight, food consumption, survival rate and incidences of clinical findings were not evident. On histopathological assessment, astrocytomas, malignant astrocytomas, oligodendrogliomas and glioblastomas were observed in the CNS, at combined incidences of 62, 67, 55 and 67% in 0, 0.002, 0.01 and 0.05% Mn treated males, respectively. None of these treated groups showed significant differences in the incidence, multiplicity or sizes of tumor as compared control group. These results indicate that offspring transplacentally exposured to ENU develop neoplasms within 34 weeks so that the present model was suggested to be useful for screening of modifiers of CNS carcinogenesis. Under the conditions tested Mn exposure did not exert any promotion potential. doi:10.1016/j.toxlet.2011.05.880

P2257 Do the aldehydes present as tobacco smoke toxicants share a common mode of action? F.H. Cunningham ∗ , S. Fiebelkorn, C. Meredith Group Research and Development, British American Tobacco, Southampton, UK Tobacco smoke contains over 5300 constituents, some with well-established toxicological properties. For a particular group of toxicants (aldehydes), we have conducted Mode of Action (MOA) reviews, using the IPCS framework. Margin of Exposure (MOE) values can be calculated for individual tobacco smoke toxicants (including many aldehydes), using EFSA guidelines. For aldehydes, the following MOE ranges have been computed: Acetaldehyde (143–1469), Formaldehyde (8–402), Acrolein (1–11), Propionaldehyde (1364–12,732). As a result, all of these aldehydes can be considered as high priorities for risk management actions. We hypothesised that the aldehyde group of tobacco smoke toxicants, as well as having similar chemical characteristics, may have common biological and toxicological properties in terms of their mode of action (MOA). This could allow for derivation of cumulative risk assessments, including application of a group MOE calculation for aldehydes. For the four aldehydes stated above, plus butyraldehyde and crotonaldehyde, the MOAs segregate between saturated and unsaturated aldehydes. Our proposed respiratory MOA for saturated aldehydes features four key events: cytotoxicity, hyperplasia, metaplasia and tumour formation, whilst for unsaturated aldehydes our proposed MOA features cytotoxicity, inflammation, hyperplasia, and metaplasia. At this stage, we cannot exclude the possibility that aldehydes have more than one MOA for respiratory tract toxicity and tumour formation. Further research modelling effective tissue dose of these toxicants in the respiratory tract of smokers will allow us to define the MOAs for aldehydes with greater clarity. doi:10.1016/j.toxlet.2011.05.881


P2258 Inhalation DNEL versus OEL to diglyme (bis(2-methoxyethyl)ether) S. Czerczak ∗ , M. Kupczewska Dobecka Chemical Safety, Nofer Institute of Occupational Medicine, Lodz, Poland Purpose: Derived inhalation No Effect Levels (DNELs) has been set for occupational exposure to bis(2-methoxyethyl)ether (diglyme) according to REACH principles. DNEL is the level of exposure above which humans should not be exposed. DNEL value was compared with occupational exposure value established in Poland to diglyme – 10 mg/m3 . Methods: Experimental data from three inhalation animal studies have been used to calculate DNELs. The main targets in male animals after repeated intake of diglyme are reproductive organs. The no-observed-adverseeffect level (NOAEL) in these studies was 30 ppm (167 mg/m3 ); the lowest-observed-adverse-effect level (LOAEL) was 100 ppm (558 mg/m3 ). In teratogenicity studies with rats diglyme showed dose-dependent effects on fetal weights, number of resorptions, and incidence of variations and malformations in a wide variety of tissues and organ systems. The LOAEL was 25 ppm (140 mg/m3 ). Changes in the haematopoietic system occurred in both sexes and involved the bone marrow, spleen, thymus, leukocytes, and erythrocytes. The NOAEL for female rats was 370 ppm (2065 mg/m3 ). The LOAEL was 1100 ppm (6138 mg/m3 ). Results of the study: Estimated DNELs values show significant differences and amount from 0.6 to 26 mg/m3 , depending on chosen critical effect. The OEL value to diglyme of 10 mg/m3 was established based on reproductive toxicity. The DNEL to reproductive is 2,2 mg/m3 . It indicates that the OEL does not provide the appropriate level of protection required by REACH. doi:10.1016/j.toxlet.2011.05.882

P2259 Medical gloves irritant contact dermatitis risk A. Eskov ∗ , R. Kaumov, A. Sokolov Firm BMK-INVEST, ZAO, Moscow, Russian Federation A few mass outbreaks of irritant contact dermatitis among medical stuff used medical gloves initiated its risk assessment. Medical gloves comprises on their surface residues of hazardous processing chemicals posing risk of irritant contact dermatitis. Latex, isoprene and nitrile medical gloves have been tested for cytotoxiciy in accordance with ISO 10993.5 to assess the risk of irritant contact dermatitis. To estimate risk extent, cytotoxicity of different extract dilutions (dilution step of 2) was evaluated. 62 brands were tested. The motility of spermatozoa suspension in control and test samples were measured by Cytotoxicity Analyzer AT-05. Cytotoxicity index was obtained in 3 h. Only 7 brands appeared not cytotoxic. Others were cytotoxic in different dilutions from 1:2 up to 1:128. It means that the extracts comprise chemicals of clinical importance of high concentration. About 75% of tested gloves were cytotoxic in dilutions higher than 1:16. Gloves which gave rise to mass irritant contact dermatitis were cytotoxic in dilution 1:32 and 1:64. The gloves surface chemicals are easy-extractable, and extraction within 15 min at 100 ◦ C can be used for risk assessment. That reduces time of whole assessment to 4 h only. Cytotoxicity testing permits the user to estimate risk quickly and to make a correct choose of medical gloves brand. The results convince that in con-


Abstracts / Toxicology Letters 205S (2011) S180–S300

formity with the European Medical Devices Directives the presence of chemicals on gloves surface must be treated as a residual risk. Users must be informed about the risk of irritant contact dermatitis by proper labeling. doi:10.1016/j.toxlet.2011.05.883

P2260 Suitability of selected software tools to evaluate the health risks of working atmosphere Z. Fiala 1,∗ , D. Drolet 2 , J. Kremlacek 3 , T. Borsky 4 , A. Vyskocil 2 , L. Borská 3 , D. Fialova 4 , V. Krajak 4 1

Charles University, Medical Faculty, Hradec Kralove, Czech Republic, 2 Département De Santé Environnementale Et Santé Au Travail, Faculté de médecine, Université de Montréal, Montreal, Canada, 3 Pathological Physiology, Charles University, Faculty of Medicine, Hradec Kralove, Czech Republic, 4 Medtec-vop spol.s r.o., Hradec Kralove, Czech Republic Purpose: Professional and scientific literature databases currently dispose a large number of important data. Effectiveness of their use is dependent on the selection and processing. Estimating the health risks of chemical exposure in the workplace depends on a sufficient number of suitable toxicological information on industrial hygiene and on reliable assessment of the exposure characteristics and scenarios. Methods: Presented software system CHEMTEK allows (1) a quick access to basic toxicological information about harmful effects of industrial chemicals and (2) modeling of time/space variations of concentrations in the working atmosphere. The system was constructed with the support of the IRSST and the EASC-AIHA. CHEMTEK integrates industrial hygiene and toxicological information from the seven databases focusing on acute and chronic effects of harmful substances. The system is able to model basic characteristics of prospective and retrospective occupational exposure in a form of 11 exposure scenarios for 630 frequent industrial pollutants. Results: The suitability and reliability of the system CHEMTEK were verified. The behavior of 22 pollutants was studied in 5 variations of exposure scenarios (experiments) and 34 contaminants were studied in short epidemiological casestudies. The results showed a very valuable gain of time and money when assessing the level of health risks in working environment (field studies). Reliability prediction of the exposure characteristics ranged between 55 and 82% (experiments). Results from the first phase of testing confirmed the suitability of CHEMTEK software system as a useful tool for assessing the health risks. Supported by CHEMTEK/OVMEDTEC20092/090183080. doi:10.1016/j.toxlet.2011.05.884

P2261 Eliciting expert knowledge about the form of the dose–response curve for genotoxic carcinogens at low exposures and the implications for a level of concern V. Flari 1,∗ , J.P. Gosling 1 , A. Hart 1 , A. Boobis 2 , E. Idahosa-Taylor 3 , L. Rushton 3 1

Science Strategy, Research And Innovation, Food and Environment Research Agency, York, UK, 2 Imperial College of Science & Technology, London, UK, 3 Imperial College, London, UK The general approach to genotoxic carcinogens has been to reduce exposure to levels that are “as low as reasonably achiev-

able” (ALARA), but this does not provide a clear basis for deciding on the urgency or extent of risk management actions. To address this, a series of international initiatives have recommended adopting a “Margin of Exposure” approach (MoE). However, a rather large (theoretically infinite) number of low dose response models for genotoxic carcinogens exist and different countries and organisations support different approaches. The models may be based on different physiological aspects regarding possible effects of genotoxic carcinogens, although they all lack a detailed, transparent, rigorous scientific rationale to justify their employment in risk assessment of genotoxic carcinogens. In a formal elicitation exercise, which included experts from both the EU and the US, we captured expert opinion on dose–response relationships for genotoxic carcinogens to assess the relative likelihood of alternative forms of dose–response and the extent to which this might vary between different classes of chemicals. We coupled this information with a systematic review of the empirical form of dose–response relationships at low exposures for genotoxic carcinogens in animals to gain a greater appreciation of what is known about low-dose extrapolation. These exercises have allowed to us to explore experts’ beliefs on the rigorous scientific rationale to support the choice among the different dose response models and to understand the interpretation of the MoEs and the associated levels of concern. doi:10.1016/j.toxlet.2011.05.885

P2262 Environmental and biological monitoring for measuring the efficacy of personal protection equipments in the use of hexavalent chromium based paints M. Gherardi 1,∗ , M.P. Gatto 1 , A. Gordiani 1 , A. Proietto 1 , E. Paci 2 , G. Tranfo 2 1

Occupational Hygiene Department, INAIL Research (formerly ISPESL), Monte Porzio Catone, Rome, Italy, 2 Occupational Medicine Department, INAIL Research (formerly ISPESL), Monte Porzio Catone, Rome, Italy Purpose: Hygienists are concerned about hexavalent chromium due to its genotoxic and carcinogenic effect on humans. This study aimed at evaluating the efficacy of the personal protection equipment (PPE) used during aircraft painting to prevent the occupational exposure to hexavalent chromium, by comparing environmental and biological monitoring. Methods: The workplace was a hangar in which an aircraft was painted with the electrospray technique. The concentration of airborne hexavalent chromium was assessed by means of personal air sampling on fibreglass filters analyzed with the NIOSH 7600 method by IC. Biological monitoring was performed analyzing the total urine chromium concentration before and after the workshift by ICP/MS. Results of the study The value of airborne hexavalent chromium found on the personal samplers worn by the painters was higher than the ACGIH exposure limit value (TLV-TWA) of 50 ␮g/m3 for Cr6+ soluble compounds (minimum 140 ␮g/m3 ), while it was lower for operators who prepared the paint. The occupational exposure to chromium evaluated only by means of the biological monitoring, due to the use of PPE, resulted for all cases lower than the ACGIH biological exposure index corresponding to an increase in the total urinary chromium concentration during the workshift of 10 ␮g/l (maximum 5.4 ␮g/l). The comparison between environmental and biological monitoring indicates that the PPE are effective in reducing the occupational exposure to hexavalent chromium but, as the urinary concentration