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Nanoparticles are emerging contaminants of concern. Knowledge on their environmental impacts is scarce, especially on their interactive effects with other contaminants. In this study we investigated effects of titanium dioxide nanoparticles (TiO2NP) on the blue mussel (Mytilus edulis) and determined their influence on the bioavailability and toxicity of benzo(a)pyrene (B(a)P), a carcinogenic polyaromatic hydrocarbon (PAH). Blue mussels were exposed to either TiO2NP (0.2 and 2.0 mg L(-1)) or B(a)P (20 μg L(-1)) and to the respective combinations of these two compounds. Aqueous contaminant concentrations, the uptake of Ti and B(a)P into mussel soft tissue, effects on oxidative stress and chromosomal damage were analyzed. The uncoated TiO2NP agglomerated rapidly in the seawater. The presence of TiO2NP significantly reduced the bioavailability of B(a)P, shown by lowered B(a)P concentrations in exposure tanks and in mussel tissue. The activities of antioxidant enzyme superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were impacted by the various exposure regimes, indicating oxidative stress in the contaminant exposure groups. While SOD activity was increased only in the 0.2TiO2NP exposure group, CAT activity was enhanced in both combined exposure groups. The GPx activity was increased only in the groups exposed to the two single compounds. In hemocytes, increased chromosomal damage was detected in mussels exposed to the single compounds, which was further increased after exposure to the combination of compounds. In this study we show that the presence of TiO2NP in the exposure system reduced B(a)P uptake in blue mussels. However, since most biomarker responses did not decrease despite of the lower B(a)P uptake in combined exposures, the results suggest that TiO2NP can act as additional stressor, or potentially alters B(a)P toxicity by activation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) are genotoxic mycotoxins that can contaminate a variety of foodstuffs, the liver and the kidney being their target organs, respectively. The micronucleus (MN) assay (bone marrow) and the comet assay (liver and kidney) were performed simultaneously in F344 rats, treated with AFB1 (0.25 mg/kg b.w.), OTA (0.5 mg/kg b.w.) or both mycotoxins. After AFB1 treatment, histopathology and biochemistry analysis showed liver necrosis, focal inflammation and an increase in Alanine Aminotransferase and Aspartate Aminotransferase. OTA alone did not cause any alteration. The acute hepatotoxic effects caused by AFB1 were less pronounced in animals treated with both mycotoxins. With regard to the MN assay, after 24 h, positive results were obtained for AFB1 and negative results were obtained for OTA, although both toxins caused bone marrow toxicity. In the combined treatment, OTA reduced the toxicity and the number of MN produced by AFB1. In the comet assay, after 3 h, positive results were obtained for AFB1 in the liver and for OTA in the kidney. The combined treatment reduced DNA damage in the liver and had no influence in the kidney. Altogether, these results may be indicative of an antagonistic relationship regarding the genotoxicity of both mycotoxins., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Alkoxyethanols (ethylene glycol alkyl ethers) are used as mixtures in a variety of industrial and household products. The aim of this study has been to evaluate the effects of 2-methoxyethanol (ME) and 2-ethoxyethanol (EE) on hematological changes induced by 2-butoxyethanol (BE) in rats., Material and Methods: Experiments were performed on male Wistar rats treated subcutaneously with BE, ME, and EE alone (in the dose of 0.75 mM/kg/day and 1.25 mM/kg/day) and their mixtures with the molar ratio 1:1, for 4 weeks. Hematological analyses were performed on the day 0, 4, 11, 18, and 29. Hemoglobin (HGB) concentration in the urine was also determined in the rats treated with BE alone and co-exposed to BE and ME and also BE and EE., Results: The rats co-exposed to BE and ME or BE and EE demonstrated significantly less pronounced hematological changes in comparison with animals treated with BE alone at the beginning of exposure. At the later period the hematological alterations in the same animals were markedly pronounced and progressing with exposure time. The rats co-exposed to BE and ME or BE and EE did not demonstrate hemoglobinuria., Conclusions: ME or EE co-administered to rats with BE lead to the amelioration in the majority of the hematological parameters at the beginning of the exposure. The hematological changes at the end of the co-exposure to BE and ME or BE and EE were markedly pronounced. The effects observed in this study appear to be related with metabolic interactions of the examined ether. Med Pr 2015;66(3):303-315., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background: We examined the risk of hearing loss for workers who use hand-held vibrating tools with vibration-induced white fingers (VWF) compared to workers without VWF., Methods: Data on 184 participants from a 21-year cohort were gathered with questionnaires and measurements. The effects on hearing status of VWF, hand-arm vibration exposure, smoking habits, age and two-way interactions of these independent variables were examined with binary logistic regression. Analyses were made for the right hand and ear as well as for the hand with VWF and the ear with worse categorized hearing status., Results: Workers with VWF in their right hand had an increased risk of hearing loss (odds ratio 2.2-2.3) in the right ear. Workers with VWF in any hand did not have any increased risk of hearing loss in the ear with worse hearing status., Conclusions: This study supports the hypothesis that VWF increases the risk of hearing loss among workers who use hand-held vibrating tools in a noisy environment., (© 2014 Wiley Periodicals, Inc.)

Bisphenol A (BPA) is employed in the manufacturing of epoxy, polyester-styrene, and polycarbonate resins, which are used for the production of baby and water bottles and reusable containers, food and beverage packing, dental fillings and sealants. The study was designed to examine the effects of 8-week exposure (a full cycle of spermatogenesis) to BPA alone and in a combination with X-irradiation on the reproductive organs and germ cells of adult and pubescent male mice. Pzh:Sfis male mice were exposed to BPA (5, 10, and 20 mg/kg) or X-rays (0.05 Gy) or to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The following parameters were examined: sperm count, sperm motility, sperm morphology, and DNA damage in male gametes. Both BPA and X-rays alone diminished sperm quality. BPA exposure significantly reduced sperm count in pubescent males compared to adult mice, with degenerative changes detected in seminiferous epithelium. This may suggest a higher susceptibility of germ cells of younger males to BPA action. Combined BPA with X-ray treatment enhanced the harmful effect induced by BPA alone in male germ cells of adult males, whereas low-dose irradiation showed sometimes protective or additive effects in pubescent mice., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.)

The effect of nonylphenol (NP; either alone or in combination with ionizing radiation) on the induction of DNA strand breaks in mouse somatic cells has been examined. Male and female mice were repeatedly irradiated with X-rays (0.05 or 0.10 Gy), injected with NP (25 or 50mg/kg bw), or both (0.05 Gy+25 mg/kg bw NP or 0.10 Gy+50 mg/kg bw NP), for 2 weeks, 5 days/week. Liver, spleen, femora, lungs and kidneys were removed from each animal for the comet assay. NP-induced DNA damage differed, depending on organ and sex. In male mice, NP induced damage in all organs examined; in females, only the kidneys were affected. The effect of irradiation alone was similar in females and males. Combined exposure of males to 0.05 Gy+25 mg/kg bw NP significantly reduced the level of DNA strand breaks, compared to the controls and to 25mg/kg bw NP alone, in the majority of organs. The higher doses significantly increased damage to DNA in all organs examined. Combined exposure of females to low doses of both agents significantly enhanced damage to DNA in bone marrow lymphocytes and in cells of the liver and kidneys, compared to controls. At 0.10 Gy+50 mg/kg bw NP, DNA damage was increased in organs except liver and spleen. Although NP alone may not be mutagenic in female mice, its co-administration with irradiation may increase DNA damage in some organs. In contrast, in male mice, damage was reduced after combined irradiation-NP exposure, compared to NP alone., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Occupational noise exposure can damage workers' hearing, particularly when combined with exposure to cochleotoxic chemicals such as styrene. Although styrene-induced cochlear impairments only become apparent after a long incubation period, the pharmacological impact of styrene on the central nervous system (CNS) can be rapidly measured by determining the threshold of the middle-ear acoustic reflex (MER) trigger. The aim of the study was to evaluate the effects of a noise (both continuous and impulse), and a low concentration of styrene [300ppm<(threshold limit value×10) safety factor] on the peripheral auditory receptor, and on the CNS in rats. The impact of the different conditions on hearing loss was assessed using distortion product oto-acoustic emissions, and histological analysis of cochleae. Although the LEX,8h (8-hour time-weighted average exposure) of the impulse noise was lower (80dB SPL sound pressure level) than that of the continuous noise (85dB SPL), it appeared more detrimental to the peripheral auditory receptors. A co-exposure to styrene and continuous noise was less damaging than exposure to continuous noise alone. In contrast, the traumatic effects of impulse noise on the organ of Corti were enhanced by co-exposure to styrene. The pharmacological effects of the solvent on the CNS were discussed to put forward a plausible explanation of these surprising results. We hypothesize that CNS effects of styrene may account for this apparent paradox. Based on the present results, the temporal structure of the noise should be reintroduced as a key parameter in hearing conservation regulations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This paper describes the structure of the Combined Environmental Stressors' Exposure (CENSE) tool. Individuals are exposed to several environmental stressors simultaneously. Combined exposure represents a more serious hazard to public health. Consequently, there is a need to address co-exposure in a holistic way. Rather than viewing chemical and physical health stressors separately for decision making and environmental sustainability considerations, the possibility of an easy-to-comprehend co-exposure assessment is herein considered. Towards this aim, the CENSE tool is developed in the programming environment of Delphi. The graphical user's interface facilitates its tractable application. Studying different scenarios is easy since the execution time required is negligible. The tool incorporates co-exposure indicators and takes into account the potential dose of each chemical stressor by considering the physical activities of each citizen in an urban (micro)environment. The capabilities of the CENSE tool are demonstrated through its application for the case of Thessaloniki, Greece. The test case highlights usability and validation insights and incorporates health stressors and local characteristics of the area considered into a well identified user/decision maker interface. The main conclusion of the work reported is that a decision maker can trust CENSE for urban planning and environmental sustainability considerations, since it supports a holistic assessment of the combined potential damage attributed to multiple health stressors. CENSE abandons the traditional approach of viewing chemical and physical stressors separately, which represents the most commonly adopted strategy in real life decision support cases., (© 2013.)

More efficient methodology for assessing the impact of combined exposures to multiple chemicals has been considered in a project of the World Health Organization (WHO) International Programme on Chemical Safety (IPCS). Recommendations regarding terminology and the status of development of the framework, its content, review and application are described. Evolving experience in its application is illustrated by example (polybrominated diphenyls) with special emphasis on the critical content of problem formulation, the role of predictive tools in grouping of chemicals for consideration and the importance of explicit delineation of relative uncertainty and sensitivity for tiered assessment. Priorities in increasing the efficiency of risk assessment not only for combined exposures, but more generally based on experience acquired in developing the framework and its application in case studies are identified and recommendations included., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The identification of the major associations of pesticides to which the population is exposed is the first step for the risk assessment of mixtures. Moreover, the interpretation of the mixtures through the individuals' diet and the characterization of potentially high-risk populations constitute a useful tool for risk management. This paper proposes a method based on Non-Negative Matrix Factorization which allows the identification of the major mixtures to which the French population is exposed and the connection between this exposure and the diet. Exposure data of the French population are provided by the Second French Total Diet Study. The NMF is implemented on consumption data to extract consumption systems which are combined with the residue levels to link dietary behavior with exposure to mixtures of pesticides. A clustering of the individuals is achieved in order to highlight clusters of individuals with similar exposure to pesticides/consumption habits. The model provides 6 main consumption systems, 6 associated mixtures of pesticides and the description of the population which is most exposed to each mixture. Two different ways to estimate the matrix providing the mixtures of pesticides to which the population is exposed are suggested. Their advantages in different contexts of risk assessment are discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method.

Procedures for risk assessment of chemical mixtures, combined and cumulative exposures are under development, but the scientific database needs considerable expansion. In particular, there is a lack of knowledge on how to monitor effects of complex exposures, and there are few reviews on biomonitoring complex exposures. In this review we summarize articles in which biomonitoring techniques have been developed and used. Most examples describe techniques for biomonitoring effects which may detect early changes induced by many chemical stressors and which have the potential to accelerate data gathering. Some emphasis is put on endocrine disrupters acting via epigenetic mechanisms and on carcinogens. Solid evidence shows that these groups of chemicals can interact and even produce synergistic effects. They may act during sensitive time windows and biomonitoring their effects in epidemiological studies is a challenging task.