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Combined Exposure (combined + exposure)

Distribution by Scientific Domains

Medical Sciences	66%
Life Sciences	20%

Selected Abstracts

Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2008
S. Christiansen
Summary The incidence of hypospadias is increasing in young boys, but it remains unclear whether human exposure to endocrine disrupting chemicals plays a role. Risk assessment is based on estimation of no-observed-adverse-effect levels for single compounds, although humans are exposed to combinations of several anti-androgenic chemicals. In a mixture (MIX) study with three androgen receptor antagonists, vinclozolin, flutamide and procymidone, rats were gavaged during gestation and lactation with several doses of a MIX of the three chemicals or the chemicals alone. External malformations of the male reproductive organs were assessed on PND 47 using a score from 0 to 3 (normal to marked) for hypospadias. Markedly increased frequencies were observed after exposure to a MIX of the three chemicals compared to administration of the three chemicals alone. Anogenital distance at PND 1, nipple retention at PND 13, and dysgenesis score at PND 16 were highly correlated with the occurrence of hypospadias, and MIX effects were seen at doses where each of the individual chemicals caused no observable effects. Therefore, the results indicate that doses of anti-androgens, which appear to induce no hypospadias when judged on their own, may induce a very high frequency of hypospadias when they interact in concert with other anti-androgens. [source]

Effects of an ethanol,gasoline mixture: results of a 4-week inhalation study in rats

JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2005
I. Chu
Abstract The inhalation toxicity of an ethanol,gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA[sol ]charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin- O -deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol,gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible biochemical hematological and histological effects, with some indications of interactions when they were co-administered. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Combined exposures to anti-androgenic chemicals: steps towards cumulative risk assessment

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010
A. Kortenkamp
Summary There is widespread exposure to anti-androgens, a group of chemicals able to disrupt androgen action in foetal life, with irreversible de-masculinizing consequences. Substances of concern include certain phthalates, pesticides and chemicals used in cosmetics and personal care products. Although people come into contact with several anti-androgens, chemicals risk assessment normally does not take account of the effects of combined exposures. However, a disregard for combination effects may lead to underestimations of risks and for this reason, we have assessed the feasibility of conducting cumulative risk assessment, where the focus is on considering the effects of exposure to multiple chemicals, via multiple routes and pathways. Following recent recommendations by the US National Research Council, we have, for the first time, included phthalates and other anti-androgenic chemicals, a total of 15 substances. On the basis of exposure estimates for the individual chemicals and reference doses for anti-androgenicity, we have used the hazard index approach. We show that the cumulative risks from anti-androgen exposures exceed acceptable levels for people on the upper end of exposure levels. The value obtained for median exposures to the 15 substances can be judged tolerable. However, significant knowledge gaps exist that prevent us from arriving at definitive conclusions. Of greatest concern is an absence of appropriate in vivo toxicity data about large numbers of in vitro androgen receptor antagonists. Knowledge about the effect profiles of these chemicals will lead to higher risk estimates. Our analysis suggests that risk reductions can be achieved by limiting exposures to the plasticizer diethyl hexyl phthalate, the cosmetic ingredients butyl- and propyl paraben, the pesticides vinclozolin, prochloraz and procymidone and bisphenol A. [source]

Proliferation and apoptosis in a neuroblastoma cell line exposed to 900 MHz modulated radiofrequency field

BIOELECTROMAGNETICS, Issue 3 2006
P. Merola
Abstract The aim of this study was to examine whether a modulated radiofrequency of the type used in cellular phone communications at a specific absorption rate (SAR) higher than International Commission on Non-ionizing Radiation Protection (ICNIRP) reference level for occupational exposure, could elicit alterations on proliferation, differentiation, and apoptosis processes in a neuroblastoma cell line. The cell line was exposed for 24, 48, and 72 h to 900 MHz radiofrequency and proliferation and differentiation were tested by WST-I assay and by a molecular analysis of specific markers, two oncogenes and a cytoskeleton protein, in exponential growth phase and in synchronized cell cultures. Apoptosis was evaluated by caspase activation analysis and by molecular detection of Poly (ADP-ribose) polimerase (PARP) cleavage. Combined exposures to radiofrequency and to the differentiative agent retinoic acid or to the apoptotic inducer camptothecin were carried out to test possible interference between electromagnetic field and chemical agents. Overall our data suggest that 900 MHz radiofrequency exposure up to 72 h does not induce significant alterations in the three principal cell activities in a neuroblastoma cell line. Bioelectromagnetics 27:164,171, 2006. © 2006 Wiley-Liss, Inc. [source]

OEESC-2005 , Summing up on the theme Irritants and Wet Work

CONTACT DERMATITIS, Issue 6 2006
Mari-Ann Flyvholm
The aim of this paper was to summarize the presentations and discussions on the theme Irritants and Wet Work at the second conference on Occupational and Environmental Exposures of Skin to Chemicals held in Stockholm June 2005 (OEESC-2005) to bring the focus points to a broader group of professionals and stimulate further discussions. Occupational skin diseases are common diseases with a huge potential for prevention. The risk factors are mostly well known, and the ongoing high occurrence of occupational skin diseases may be seen as a paradox problem. Although all mechanisms involved in occupational skin diseases are not shown throughout, much is known. The existing knowledge justifies the relevance of reducing exposure and introducing prevention programmes. The questions identified for further research included an internationally agreed-upon definition of wet work; better methods to assess the exposure to wet work; the effect of combined exposure to water and water-soluble irritants; the importance of wet work with frequent/short wet,dry cycles versus working longer periods with wet hands; testing skin protection and skin care products; long-term skin effects from alcohol-based hand disinfectants; workplace testing of evidence-based prevention programmes in prospective randomized, controlled intervention studies. [source]

Augmentation of skin response by exposure to a combination of allergens and irritants , a review

CONTACT DERMATITIS, Issue 5 2004
Line Kynemund Pedersen
Clinical experimental studies on contact dermatitis (CD) often evaluate the effect of one allergen or one irritant at a time. In real life, the skin is often exposed to more allergens, more irritants or allergens and irritants in combination. This combined exposure may potentially influence irritant effects as well as allergenicity of the substances. Mechanisms for a changed response can be immunological effects or enhanced penetration. Knowledge about the influence on skin reaction of combined exposures may influence skin reactivity and is important for prevention of CD. For allergens, threshold values may be influenced by the presence of other allergens or irritants, and prevention of CD by regulation of threshold values may not be sufficient if this is not taken into account. [source]

Synergistic genotoxicity caused by low concentration of titanium dioxide nanoparticles and p,p,-DDT in human hepatocytes

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2010
Yun Shi
Abstract The use of titanium dioxide nanoparticles (nano-TiO2) for the degradation of dichlorodiphenyltrichloroethane (p,p,-DDT) increases the risk of exposure to trace nano-TiO2 and p,p,-DDT mixtures. The interaction of p,p,-DDT and nano-TiO2 at low concentrations may alter toxic response relative to nano-TiO2 or p,p,-DDT alone. In this work, the combined genotoxicity of trace nano-TiO2 and p,p,-DDT on human embryo L-02 hepatocytes without photoactivation was studied. Nano-TiO2 (0.1 g/L) was mixed with 0.01,1 mmol/L p,p,-DDT to determine adsorption isotherms. L-02 cells were exposed to different levels of p,p,-DDT (0, 0.001, 0.01, and 0.1 ,mol/L) and nano-TiO2 (0, 0.01, 0.1, and 1 ,g/mL) respectively. The adsorption of p,p,-DDT by nano-TiO2 was approximately 0.3 mmol/g. Cell viability, apoptosis, and DNA double strand breaks were similar among all test groups. Nano-TiO2 alone (0.01,1 ,g/mL) increased the levels of oxidative stress and oxidative DNA adducts (8-OHdG), but it did not induce DNA breaks or chromosome damage. Addition of trace nano-TiO2 with trace p,p,-DDT synergistically enhanced genotoxicity via increasing oxidative stress, oxidative DNA adducts, DNA breaks, and chromosome damage in L-02 cells. Low concentrations of nano-TiO2 and p,p,-DDT increased oxidativestress by reactive oxygen species (ROS) formation and lipid oxidation. Oxidative stress is a major pathway for DNA and chromosome damage. Dose-dependent synergistic genotoxicity induced by combined exposure of trace p,p,-DDT and nano-TiO2 suggests a potential environmental risk of nano-TiO2 assisted photocatalysis. Environ. Mol. Mutagen., 2010. © 2009 Wiley-Liss, Inc. [source]

Dendritic cell activation by combined exposure to anti-CD40 plus interleukin (IL)-12 and IL-18 efficiently stimulates anti-tumor immunity

EXPERIMENTAL DERMATOLOGY, Issue 1 2009
Sandra Balkow
Abstract:, Despite as yet limited clinical effectiveness, dendritic cell (DC)-based immunotherapy remains a promising approach for the treatment of cancer, but requires further improvement in its immunostimulatory effectiveness. Potent anti-tumor immunity often depends on the induction of type 1 (TH1) immune responses. Therefore, we combined different DC maturation stimuli that are known to induce TH1 immunity [anti-CD40, interleukin (IL)-12, IL-18], with the aim to trigger a TH1 driven anti-tumor CTL response. When compared with untreated DC or DC treated with anti-CD40 alone, DC matured with anti-CD40 plus IL-12 and IL-18 expressed significantly more IFN-, and IL-12, induced enhanced CD8+ T-cell proliferation, prolonged synaptic interaction with T cells and increased CD8+ T-cell-mediated cytotoxicity. To analyse if these DC are able to induce efficient anti-tumor immunity, mice carrying a B16-OVA tumor were treated with tumor antigen (TA)-loaded DC that had been exposed to anti-CD40 or to anti-CD40 plus IL-12 and IL-18. Our data show that anti-CD40 plus IL-12 and IL-18 matured DC are superior to controls in retarding tumor growth. These data indicate that maturation of DC with anti-CD40 plus IL-12 and IL-18 potently stimulates the generation of an anti-tumor immune response and may lead to improved immunotherapeutic capacity of DC vaccination. [source]

Combined pulmonary toxicity of cadmium chloride and sodium diethyldithiocarbamate

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001
Erzsébet Tátrai
Abstract The pulmonary toxicity of sodium diethyldithiocarbamate and cadmium chloride, each separately and in combination, was compared in Sprague-Dawley rats after single intratracheal instillation in sequential experiments by chemical, immunological and morphological methods. With combined exposure, the cadmium content of the lungs increased permanently relative to that of the lungs of just cadmium-treated animals. Immunoglobulin levels of the whole blood did not change, whereas in bronchoalveolar lavage the IgA and IgG levels increased significantly. Morphological changes were characteristic of the effects of cadmium but were more extensive and more serious than in the case of cadmium administration alone: by the end of the first month, interstitial fibrosis, emphysema and injury of membranes of type I pneumocytes developed and hypertrophy and loss of microvilli in type II pneumocytes were detectable. These results showed that although dithiocarbamates as chelating agents are suitable for the removal of cadmium from organisms, they alter the redistribution of cadmium within the organism, thereby increasing the cadmium content in the lungs, and structural changes are more serious than observed upon cadmium exposure alone. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Geographic Information Systems: A New Tool for Environmental Health Assessments

PUBLIC HEALTH NURSING, Issue 5 2006
Mona Choi
ABSTRACT Objectives: (1) To develop tools for health care professionals and communities to assess environmental exposures and (2) to evaluate the utility of integrating patient-reported environmental health information with geographic information systems (GIS) mapping of environmental data in a pilot study. Methods: A survey was used to collect self-reported environmental exposure and health data from a convenience sample of people at an urban community health center (N=101). Environmental exposure and census information were obtained from federal agencies. Analysis was performed using descriptive statistics and GIS. Results: Frequent environmental health risk factors were reported, such as older housing (93%) and household smoking (78%). Health problems including asthma (54%) and lead poisoning (14%) were reported. Odds ratios indicated a statistically significant relationship between mold/mildew and reporting asthma. GIS was found to be a useful tool in displaying environmental risk factors and potentially associated health effects. Conclusions: Given the important role that environmental health risks can play in public health, it is critical that community/public health nurses begin to integrate environmental health assessment skills into their professional practices. Simple community surveys can be an effective means to raise awareness about environmental health risk factors and utilizing GIS can further enhance the accessibility of the combined exposure and health information. [source]

Combined cell wall polysaccharide, mycotoxin and bacterial lipopolysaccharide exposure and inflammatory cytokine responses

APMIS, Issue 7 2009
LENE JOHANNESSEN
Human exposure to environmental microbes occurs regularly. Microbial compounds may interact with each other to affect cellular responses. We hypothesized that interactions between microbial compounds could modulate inflammatory cytokine responses in vitro. We investigated monocyte production of the pro-inflammatory cytokine tumour necrosis factor-, (TNF-,) and the regulatory cytokine interleukin-10 (IL-10) after combined exposure to the fungal cell wall polysaccharide mannan and to the ,-glucan laminarin, the mycotoxin citrinin and bacterial lipopolysaccharide (LPS). Interactions between the cell wall microbial compounds were estimated statistically in a general linear mixed model. We found that LPS (100 ng/ml) and the used ,-glucan (up to 1000 ,g/ml) significantly interacted with each other to reduce TNF-, production. Mannan (up to 100 ,g/ml) did not interact with the ,-glucan, but interacted with LPS. IL-10 production was induced by LPS only. The mycotoxin citrinin did not induce cytokine production, but was toxic to the cells in a dose- and time-dependent manner. However, non-toxic doses of citrinin reduced LPS-induced IL-10 production while LPS-induced TNF-, production was not similarly reduced by citrinin. In conclusion, interactions between microbial compounds can modulate cellular inflammatory cytokine production and experimental investigations of one compound at a time could give misleading conclusions about these combined effects. [source]

Sequential application of cold and sodium lauryl sulphate decreases irritation and barrier disruption in vivo in humans

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2005
J.W. Fluhr
Summary Background, Irritant contact dermatitis (ICD) is one of the most frequent types of occupational dermatitis. Different factors are involved in the development of contact dermatitis. In the food-processing industry, the combined exposure to different irritants may be involved in the development of ICD. Few data have been published regarding the irritant potential of sodium lauryl sulphate (SLS) in combination with cold. Objectives, The present study was intended to analyse whether cold exposure and low skin temperature influence the development of ICD. Methods, Twenty (part I) and 12 (part II) healthy volunteers were exposed twice daily for 4 days to SLS alone, different low temperatures alone (4 °C six times for 90 s with an interval of 20 s or 15 °C for 10 min) or a combination of cold and SLS (19·6 µL SLS 1% cm,2, part I; or 52·6 µL SLS 0·5% cm,2, part II) using the tandem repetitive irritation test. Irritant cutaneous reactions were measured by noninvasive biophysical methods with transepidermal water loss as a parameter for permeability barrier function and skin colour reflectance together with visual scoring as parameters for inflammatory reactions. Results, Cold alone caused no significant skin reaction compared with untreated control. Exposure to SLS alone and SLS together with cold (independent of the applied temperature of 4 or 15 °C) twice daily induced a clear irritant reaction and barrier disturbance. Reactions did not differ whether SLS was applied before or after cold. Furthermore, ,tandem application' of cold and SLS diminished the barrier disruption and irritant reaction compared with SLS alone. Conclusions, We conclude that the application of cold may have a protective effect on the development of ICD, at least in our short-term model. [source]

Augmentation of skin response by exposure to a combination of allergens and irritants , a review

Combined exposures to anti-androgenic chemicals: steps towards cumulative risk assessment

Reactive oxygen species formation is not enhanced by exposure to UMTS 1950 MHz radiation and co-exposure to ferrous ions in Jurkat cells

BIOELECTROMAGNETICS, Issue 7 2009
Francesca Brescia
Abstract This study was designed to assess if radiofrequency (RF) radiation induces oxidative stress in cultured mammalian cells when given alone or in combination with ferrous ions (FeSO4). For this purpose the production of reactive oxygen species (ROS) was measured by flow cytometry in human lymphoblastoid cells exposed to 1950 MHz signal used by the third generation wireless technology of the Universal Mobile Telecommunication System (UMTS) at Specific Absorption Rate of 0.5 and 2.0 W/kg. Short (5,60 min) or long (24 h) duration exposures were carried out in a waveguide system under strictly controlled conditions of both dosimetry and environment. Cell viability was also measured after 24 h RF exposure using the Resazurin and Neutral Red assays. Several co-exposure protocols were applied to test if RF radiation is able to alter ROS formation induced by FeSO4 (RF given before or concurrently to FeSO4). The results obtained indicate that non-thermal RF exposures do not increase spontaneous ROS formation in any of the experimental conditions investigated. Consistent with the lack of ROS production, no change in cell viability was observed in Jurkat cells exposed to RF radiation for 24 h. Similar results were obtained when co-exposures were considered: combined exposures to RF radiation and FeSO4 did not increase ROS formation induced by the chemical treatment alone. In contrast, in cultures treated with FeSO4 as positive control, a dose-dependent increase in ROS formation was recorded, validating the sensitivity of the method employed. Bioelectromagnetics 30:525,535, 2009. © 2009 Wiley-Liss, Inc. [source]