Exposure Levels (exposure + level)

Distribution by Scientific Domains
Distribution within Life Sciences


Selected Abstracts


Calculated Ultraviolet Exposure Levels for a Healthy Vitamin D Status

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006
Ann R. Webb
The dangers of overexposure to sunlight have been well publicized, but less attention has been given to an acknowledged benefit of exposure to UV radiation; that being the cutaneous synthesis of vitamin D3. Here we define a standard vitamin D dose on the basis of recently recommended requirements for vitamin D that take account of its risk reduction role in a variety of diseases, and present a web-based tool that enables the reader to calculate associated exposure times for any time and place using either default values or user-selected conditions. Either it is not possible to synthesize vitamin D3 at high latitudes in winter, or the exposure time required to reach a standard dose is sometimes impractical. Where solar UV is sufficient, a risk-benefit analysis of sunburn vs. vitamin D3 synthesis shows that the best time for brief sun exposure is in the middle of the day. For low solar elevation angles common at high latitudes, a fine line exists between adequate UV exposure for vitamin D3 synthesis and a risk of sun burn. [source]


Exposure of children and adolescents to alcohol advertising on Australian metropolitan free-to-air television

ADDICTION, Issue 7 2009
Lynda Fielder
ABSTRACT Aim This study investigated the exposure of underage youth to alcohol television advertising on metropolitan free-to-air television in the five mainland capital city markets of Australia. Design Exposure levels (target audience rating points; TARPs) were obtained for all alcohol advertisements screened from November 2005 to October 2006 in each capital city market for: children 0,12 years; underage teens 13,17 years; young adults 18,24 years; and mature adults 25+ years. The 30 most exposed advertisements across age groups were then content-analysed for elements appealing to children and underage youth. Results In each of the five metropolitan markets, mature adults were most exposed to alcohol advertising. Children were exposed to one-third the level of mature adults and underage teens to approximately the same level as young adults. However, there was considerable variation in media weight between markets, such that underage teens in two markets had higher advertising TARPs than young adults in other markets. All 30 highest exposed advertisements contained at least one element known to appeal to children and underage youth, with 23 containing two or more such elements. Fifteen of the 30 advertisements featured an animal. Conclusions The self-regulation system in Australia does not protect children and youth from exposure to alcohol advertising, much of which contains elements appealing to these groups. [source]


The association between socioeconomic status and exposure to mobile telecommunication networks in children and adolescents

BIOELECTROMAGNETICS, Issue 1 2010
Silke Thomas
Abstract A potential association between socioeconomic status (SES) and self-reported use of mobile phones has been investigated in a few studies. If measured exposure to mobile phone networks differs by SES in children, it has not yet been studied. Interview data of 1,481 children and 1,505 adolescents on participants' mobile phone use, socio-demographic characteristics and potential confounders were taken from the German MobilEe-study. Sociodemographic data was used to stratify participants into three "status groups" (low, middle, high). Using a personal dosimeter, we obtained an exposure profile over 24,h for each of the participants. Exposure levels during waking hours were expressed as mean percentage of the reference level. Children with a low SES were more likely to own a mobile phone (OR 2.1; 95% CI: 1.1,3.9) and also reported to use their mobile phone longer per day (OR 2.4; 95% CI: 1.1,5.4) than children with a high SES. For adolescents, self-reported duration of mobile phone use per day was also higher with a low SES (OR: 3.4; 95% CI: 1.4,8.4) compared with a high SES. No association between SES and measured exposure to mobile telecommunication networks was seen for children or adolescents. Mobile phone use may differ between status groups with higher use among disadvantaged groups. However, this does not result in higher overall exposure to mobile telecommunication networks. Whether short duration of own mobile phone use or the small numbers of participants with a low SES are causal, have to be investigated in further studies. Bioelectromagnetics 31:20,27, 2010. © 2009 Wiley-Liss, Inc. [source]


Principles of risk assessment for determining the safety of chemicals: Recent assessment of residual solvents in drugs and di(2-ethylhexyl) phthalate

CONGENITAL ANOMALIES, Issue 2 2004
Ryuichi Hasegawa
ABSTRACT Risk assessment of chemicals is essential for the estimation of chemical safety, and animal toxicity data are typically used in the evaluation process, which consists of hazard identification, dose,response assessment, exposure assessment, and risk characterization. Hazard identification entails the collection of all available toxicity data and assessment of toxicity endpoints based on findings for repeated dose toxicity, carcinogenicity or genotoxicity and species-specificity. Once a review is compiled, the allowable lifetime exposure level of a chemical is estimated from a dose,response assessment based on several measures. For non-carcinogens and non-genotoxic carcinogens, the no-observed-adverse-effect-level (NOAEL) is divided by uncertainty factors (e.g. with environmental pollutants) or safety factors (e.g. with food additives) to derive a tolerable daily intake (TDI) or acceptable daily intake (ADI), respectively. These factors include interspecies and individual differences, duration of exposure, quality of data, and nature of toxicity such as carcinogenicity or neurotoxicity. For genotoxic carcinogens, low dose extrapolation is accomplished with mathematical modeling (e.g. linearized multistage model) from the point of departure to obtain exposure levels that will be associated with an excess lifetime cancer risk of a certain level. Data for levels of chemicals in food, water and air, are routinely used for exposure assessment. Finally, risk characterization is performed to ensure that the established ,safe' level of exposure exceeds the estimated level of actual exposure. These principles have led to the evaluation of several existing chemicals. To establish a guideline for residual solvents in medicine, the permitted daily exposure (PDE), equivalent to TDI, of N,N-dimethylformamide was derived on the basis of developmental toxicity (malformation) and of N-methylpyrrolidone on the basis of the developmental neurotoxicity. A TDI for di(2-ethylhexyl)phthalate was derived from assessment of testicular toxicity. [source]


DNA damage and TNF, cytokine production in hairdressers with contact dermatitis

CONTACT DERMATITIS, Issue 3 2005
Delia Cavallo
The present work was undertaken to study in hairdressers exposed to several irritants and allergens (prevalently hair-dyeing) and affected by hand contact dermatitis the possible correlation between exposure and direct-oxidative DNA damage, production of tumour necrosis factor alpha (TNF,) and allergic inflammatory disease. We evaluated in 19 hairdressers with hand contact dermatitis, 14 allergic contact dermatitis (ACD) and 5 irritant contact dermatitis (ICD) and in a selected control group TNF, serum levels by ELISA and direct-oxidative DNA damage by Fpg (formamido-pyrimidine-glycosylase)-modified Comet test on blood. Hairdressers were divided on the basis of number of hair-dyeing carried out weekly into 2 groups: low-exposure (<60 hair-dyeing/week) and high-exposure hairdressers (,60 hair-dyeing/week) that reflect also the exposure to other allergens and irritants and 2 different tasks (hairdressers and apprentice hairdressers, respectively). Serum levels of TNF, in hairdressers with ACD were significantly higher than controls with a correlation to exposure level. Significant DNA damage in ICD hairdressers with higher exposure as compared to controls was found. These findings suggest that occupational exposure can induce in hairdressers, particularly ICD, DNA damage, increase the TNFa levels particularly in ACD and induce allergic sensitization, suggesting a relationship between direct-oxidative DNA damage, TNF, production and allergic inflammatory disease. [source]


Statistical issues on the determination of the no-observed-adverse-effect levels in toxicology

ENVIRONMETRICS, Issue 4 2001
Takashi Yanagawa
Abstract The determination of a safe exposure level for toxic agents, often defined as the highest dose level with no toxic effect and termed the no-observed-adverse-effect level (NOAEL) is reviewed. The conventional methods based on statistical tests are criticized, particularly when the sample size is small, and an alternative method, which is based on the Akaike information criterion (AIC), is discussed. The method is extended to the estimation of the NOAEL for continuous data. Computer programs for Windows 95/NT for determining the NOAEL by the AIC approach are developed and its application to practical data is illustrated with examples. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Application of a one-dimensional thermal flame spread model on predicting the rate of heat release in the SBI test

FIRE AND MATERIALS, Issue 2 2001
Tuula Hakkarainen
A one-dimensional thermal flame spread model was applied to predict the rate of heat release in the single burning item (SBI) test on the basis of the cone calorimeter data. The input parameters were selected according to the features of the SBI test and using particle board as a model tuning material. The features of the measured and calculated rate of heat release curves were compared for a series of 33 building products. The fire growth rate (FIGRA) indices were calculated to predict the classification in the forthcoming Euroclass system. The model gave correct classification for 90% of the products studied. An essential feature of the model is that only one cone calorimeter test at the exposure level of 50 kW m,2 is needed. The model, therefore, provides a practical tool for product development and quality control. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Breast cancer and microbial cancer incidence in female populations around the world: A surprising hyperbolic association

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2008
Anamaria Savu
Abstract Current literature on cancer epidemiology typically discusses etiology of cancer by cancer type. Risks of different cancer types are, however, correlated at population level and may provide etiological clues. We showed previously an unexpected very high positive correlation between breast cancer (BC) and young-adult Hodgkin disease incidence rates. In a population-based case,control study of BC, older ages at the first Epstein,Barr virus exposure, indicated by older ages at onset of infectious mononucleosis, were associated with elevated BC risk. Here we examine BC risk in association with microbial cancer (MC) risk in female populations across the world. MC cancers are cervical, liver and stomach cancers with established causal associations with human papillomaviruses, hepatitis viruses, and helicobacter pylori, respectively. We examined age-adjusted BC and MC incidence rates in 74 female populations around the world with cancer registries. Our analysis suggests that BC and MC rates are inversely associated in a special mathematical form such that the product of BC rate and MC rate is approximately constant across world female populations. A differential equation model with solutions consistent to the observed inverse association was derived. BC and MC rates were modeled as functions of an exposure level to unspecified common factors that influence the 2 rates. In conjunction with previously reported evidence, we submit a hypothesis that BC etiology may have an appreciable link with microbial exposures (and/or immunological responses to them), the lack of which, especially in early life, may elevate BC risk. © 2008 Wiley-Liss, Inc. [source]


Transmission of neozoic Anguillicoloides crassus and established Camallanus lacustris in ruffe Gymnocephalus cernuus

JOURNAL OF FISH BIOLOGY, Issue 9 2008
J. Unger
In the present study, groups of ruffe Gymnocephalus cernuus, reared singly, were exposed to defined numbers of Anguillicoloides crassus or Camallanus lacustris under controlled laboratory conditions. Infection took place orally through feeding G. cernuus with axenically cultured and laboratory infected copepods, in which the parasites had developed to the infective third stage (L3). Mean prevalence (94·3%) and infection probability (38·5%) for the established C. lacustris were significantly higher than for the neozoic A. crassus (14·3 and 1·0%, respectively). Peripheral blood leukocytes were significantly increased in infected fish, apparently independent of exposure level, parasite species or intensity of infection compared to the controls. In infected fish, the gonado-somatic index (IG) was significantly reduced by c. 50%, and the spleen-somatic index (IS) was significantly increased compared to controls. Both parasites raised similar physiological and immunological responses in G. cernuus, which was able to effectively reject the neozoic A. crassus. [source]


Complementary and alternative medicine inclusion in physical therapist education in the United States

PHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 4 2009
Paula Richley Geigle
Abstract Purpose.,The purpose of this study was to determine the current prevalence, and at what level, complementary and alternative medicine (CAM) content is included in physical therapist (PT) education in the United States. This survey study provides self-report data regarding reasons why faculty members choose to include or not include CAM into programme content.,Background/Significance.,This study investigates the current prevalence of CAM content, and what level of inclusion (minimal, moderate, advanced) in PT curricula will assist programmes as they modify existing curricula and develop new programmes.,Subjects.,All 196 US-accredited programmes were included in our survey.,Materials and Methods.,An IRB-approved (Investigational Review Board), pilot-tested, two-page survey was emailed to all programme chairpersons of accredited PT programmes. A hard copy survey was mailed to non-responding programmes.,Analyses.,Returned surveys were analyzed descriptively to characterize the data shape, tendency and variability. Data were summarized in a frequency distribution and graphically depicted in a histogram for each category. In addition, qualitative analysis was completed for the explanatory data.,Results.,Forty-seven per cent (92) of all accredited PT programmes (196) responded. Most commonly included CAM areas were: manipulative and body-based methods, alternative medical systems and biologically based therapies. Most frequent responses to limitations to including CAM in PT curriculum were: limited curriculum time, lack of evidence supporting CAM practices and trouble locating qualified CAM presenters.,Conclusions.,This survey suggests the following: CAM techniques are included in entry-level PT education in the United States; the majority of these techniques are offered at the minimum or exposure level; manipulative and body-based methods, alternative medical systems and biologically based therapies are the most frequently included CAM techniques. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Assessment of airborne and dermal exposure to 2-ethoxyethyl acetate in an occupational environment,

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 8 2009
Tung-Sheng Shih ScD
Abstract Background Because of its chemical,physical properties, 2-ethoxyethyl acetate (EEAc) can penetrate through the skin. However, no actual occupational environmental studies or empirical dermal exposure measurements have been performed. Methods Twenty workers from a commercial label silk screening shop were recruited and they completed a questionnaire of demographic information. Environmental monitoring of EEAc exposure via respiratory and dermal routes was performed for five consecutive working days. Results Airborne EEAc concentration was over the permissible exposure limit of 5,ppm in 90% of the participants. The dermal EEAc concentration was highest on the palms. The EEAc concentration correlated with skin exposure level (P,<,0.001). The dermal EEAc concentrations in individuals who did not wear gloves were higher than in those who wore gloves. Conclusions EEAc on the skin is strongly associated with airborne EEAc. Wearing impermeable gloves during high-risk tasks (cleaning process) can reduce EEAc dermal exposure on the palms. Am. J. Ind. Med. 52:654,661, 2009. © 2009 Wiley-Liss, Inc. [source]


Epistaxis in a low level hydrogen fluoride exposed industrial staff

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 3 2009
Pål Graff
Abstract Objectives To assess the effect of exposure to hydrogen fluoride (HF) on the airway mucosa in an industrial setting. Methods A cross-sectional study encompassing 33 industrial workers in a flame soldering plant and 44 assembly workers unexposed to HF was performed by means of a questionnaire on symptoms and diagnosis regarding upper and lower airways as well as through conduct of a clinical examination of the exposed group. Air concentrations of HF that were monitored in winter amounted to 1.0 mg/m3 and in summer time to 0.15 mg/m3. Results A threefold risk for epistaxis (RR,=,3.6, 95% confidence interval 1.1,11.0) was observed in the exposed group. Time from the start of exposure to HF until debut of a nose bleeding period varied from 1 month to 6 years. Mean induction (latency) time was 42 months. Mean duration of symptoms was 26 months, range 3,72 months, indicating that the exposure level in summer time was sufficient to maintain the propensity of almost daily nose bleeding. Conclusion HF is an irritating vapor, even at relatively low air concentrations. We recommend an 8 hr TLV lower than 1.0 mg/m3. Am. J. Ind. Med. 52:240,245, 2009. © 2008 Wiley-Liss, Inc. [source]


Maternal nickel exposure and congenital musculoskeletal defects

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 11 2008
Vaktskjold Arild DrScient
Abstract Objective To investigate whether women occupationally exposed to nickel in early pregnancy are at elevated risk of delivering a newborn with a malformation or deformation of the musculoskeletal system (ICD-10: Q65-Q79). Methods Data about the newborn, maternal occupation and workplace were obtained using the Kola Birth Register (KBR). Each record in the KBR was assigned a categorical nickel (Ni) exposure rating according to the occupation the delivering woman had at the time of becoming pregnant. This was achieved by using as a guideline the water-soluble Ni subfraction of the inhalable aerosol fraction obtained by personal monitoring for nickel- and copper-refinery workers or/and measured urinary-Ni concentrations. The reference population was delivering women from the source population with background exposure level. In total, the study population consisted of 22,965 births. Results Three hundred and four infants (13.3/1,000 births; 95% confidence interval (CI): 11.9,14.7) were diagnosed with isolated musculoskeletal defect(s) at birth. The adjusted odds ratio for the association between the maternal exposure to Ni and this outcome was 0.96 (95% CI: 0.76,1.21) per unit increase in exposure category. Conclusion The incidence of defects in the musculoskeletal system at birth was high, especially for feet deformities, but we found no effect of maternal exposure to water-soluble Ni on the risk of delivering a newborn with a defect. However, the incidence among women working in the copper refinery was higher than in the other employment groups. Am. J. Ind. Med. 51:825-833, 2008. © 2008 Wiley-Liss, Inc. [source]


Chronologic Changes of Nitric Oxide Concentration in the Cochlear Lateral Wall and Its Role in Noise-Induced Permanent Threshold Shift

THE LARYNGOSCOPE, Issue 5 2008
Yuh-Shyang Chen MD
Abstract Objective: The objective of this study was to investigate the chronologic changes of nitric oxide (NO) concentration in the cochlear lateral wall and to explore its possible role in permanent threshold shift (PTS) after intense noise exposure. Materials and Methods: Seventeen guinea pigs were subjected to a single continuous exposure to broadband white noise at 105 ± 2 dB sound pressure level (SPL) for 40 hours and were divided into four groups according to various postnoise recovery periods. Another 12 guinea pigs were not exposed to noise and served as controls. The hearing status of all animals was evaluated with auditory brainstem responses (ABR) evoked by condensation "click" sounds. ABR were recorded both prior to noise exposure and immediately before killing the animal. After death, NO concentration in the cochlear lateral wall was directly measured with an NO/ozone chemiluminescence technique. Results: An approximately 1.7-fold increase in NO concentration was observed immediately postnoise exposure, which persisted for up to 28 days. The threshold of ABR elevation (mean, 30 dB SPL) peaked immediately after cessation of noise exposure and gradually resolved to a PTS (mean, 14.5 dB SPL) 56 days after noise exposure when NO concentration had returned to its prenoise exposure level. Conclusion: Noise-induced threshold shift, which resolved to a mild PTS, can be partially attributed to NO elevation in the cochlear lateral wall. Our results revealed a nonlinear correlation between ABR recovery and depletion of NO, indicating that the mechanisms of NO changes in the cochlear lateral wall may be more complicated than previously conceived and that other pathophysiologic mechanisms may also play important roles in noise-induced PTS. [source]


Candidate Gene Association Study for Noise-induced Hearing Loss in Two Independent Noise-exposed Populations

ANNALS OF HUMAN GENETICS, Issue 2 2009
A. Konings
Summary Millions of people are daily exposed to high levels of noise. Consequently, noise-induced hearing loss (NIHL) is one of the most important occupational health hazards worldwide. In this study, we performed an association study for NIHL based on a candidate gene approach. 644 Single Nucleotide Polymorphisms (SNPs) in 53 candidate genes were analyzed in two independent NIHL sample sets, a Swedish set and part of a Polish set. Eight SNPs with promising results were selected and analysed in the remaining part of the Polish samples. One SNP in PCDH15 (rs7095441), resulted in significant associations in both sample sets while two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. Calculation of odds ratios revealed a significant association of rs588035 with NIHL in the Swedish high noise exposure level group. Our studies suggest that PCDH15 and MYH14 may be NIHL susceptibility genes, but further replication in independent sample sets is mandatory. [source]


Estimation of relative exposure levels for cellular phone users using a neural network

BIOELECTROMAGNETICS, Issue 6 2006
Soo Chan Kim
Abstract The wide and growing use of cellular phones has raised questions about the possible health risks associated with radio frequency (RF) electromagnetic fields. It would be helpful for epidemiologists as well as cellular phone users to obtain the relative exposure levels, because the RF exposure level is very difficult to accurately measure and quantify for all individuals. In this study, a neural network model was developed to estimate relative exposure levels on a scale of 0,10 and thus rank the individual risk of exposure using available information. We used parameters such as usage time per day, total usage period, hands-free usage, extension of antenna, specific absorption rate (SAR) of the cellular phone, and flip or folder type, which are related to RF exposure. Using the relative exposure levels obtained from this model, epidemiologists can divide the subjects into exposed and nonexposed groups in a study investigating the relationship between exposure level and brain cancer in the future, provided that more knowledge between the cellular phone usage pattern and the exposure is available. Bioelectromagnetics 27:440,444, 2006. © 2006 Wiley-Liss, Inc. [source]


Principles of risk assessment for determining the safety of chemicals: Recent assessment of residual solvents in drugs and di(2-ethylhexyl) phthalate

CONGENITAL ANOMALIES, Issue 2 2004
Ryuichi Hasegawa
ABSTRACT Risk assessment of chemicals is essential for the estimation of chemical safety, and animal toxicity data are typically used in the evaluation process, which consists of hazard identification, dose,response assessment, exposure assessment, and risk characterization. Hazard identification entails the collection of all available toxicity data and assessment of toxicity endpoints based on findings for repeated dose toxicity, carcinogenicity or genotoxicity and species-specificity. Once a review is compiled, the allowable lifetime exposure level of a chemical is estimated from a dose,response assessment based on several measures. For non-carcinogens and non-genotoxic carcinogens, the no-observed-adverse-effect-level (NOAEL) is divided by uncertainty factors (e.g. with environmental pollutants) or safety factors (e.g. with food additives) to derive a tolerable daily intake (TDI) or acceptable daily intake (ADI), respectively. These factors include interspecies and individual differences, duration of exposure, quality of data, and nature of toxicity such as carcinogenicity or neurotoxicity. For genotoxic carcinogens, low dose extrapolation is accomplished with mathematical modeling (e.g. linearized multistage model) from the point of departure to obtain exposure levels that will be associated with an excess lifetime cancer risk of a certain level. Data for levels of chemicals in food, water and air, are routinely used for exposure assessment. Finally, risk characterization is performed to ensure that the established ,safe' level of exposure exceeds the estimated level of actual exposure. These principles have led to the evaluation of several existing chemicals. To establish a guideline for residual solvents in medicine, the permitted daily exposure (PDE), equivalent to TDI, of N,N-dimethylformamide was derived on the basis of developmental toxicity (malformation) and of N-methylpyrrolidone on the basis of the developmental neurotoxicity. A TDI for di(2-ethylhexyl)phthalate was derived from assessment of testicular toxicity. [source]


Evaluation of 2 self-administered questionnaires to ascertain dermatitis among metal workers and its relation with exposure to metalworking fluids

CONTACT DERMATITIS, Issue 6 2007
Berna Van Wendel de Joode
We performed an exploratory study to evaluate 2 self-administered questionnaires assessing hand dermatitis and investigate a possible exposure,response relationship between dermal exposure to semi-synthetic metalworking fluids (SMWF) and dermatitis. In a cross-sectional survey on dermatitis, a symptom-based questionnaire and a picture-based skin screening list were applied in 80 SMWF-exposed workers and 67 referents. To evaluate the accuracy of the questionnaires, 47 subjects were examined by a dermatologist. Dermal exposure levels to SMWF were assessed on hands, forearms, and face with a observational method that was validated using a fluorescent tracer method. The symptom-based questionnaire had a relatively high sensitivity (0.86) but moderate specificity (0.64), and the skin screening list had a low sensitivity (0.36) and a relatively high specificity (0.84). The skin screening list seemed to represent the more severe cases of dermatitis and showed a significant relation with exposure for dermatitis on hands, forearms, or face. In epidemiological surveys where workers are not seen by a dermatologist, the skin screening list seems to be more appropriate to detect cases of dermatitis, as its higher specificity results in less false positives. Alternatively, it would be preferable applying the symptom-based questionnaire; workers with symptoms should be seen by a dermatologist to identify false positives. [source]


Molecular analysis of mutations at the HPRT and TK loci of human lymphoblastoid cells after combined treatments with 3,-azido-3,-deoxythymidine and 2,,3,-dideoxyinosine,

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2002
Quanxin Meng
Abstract Combinations of antiretroviral drugs that include nucleoside reverse transcriptase inhibitors (NRTIs) are superior to single-agent regimens in treating or preventing HIV infection, but the potential long-term health hazards of these treatments in humans are uncertain. In earlier studies, our group found that coexposure of TK6 human lymphoblastoid cells to 3,-azido-2,,3,-dideoxythymidine (AZT) and 2,,3,-dideoxyinosine (ddI), the first two NRTIs approved by the FDA as antiretroviral drugs, produced multiplicative synergistic enhancement of DNA incorporation of AZT and mutagenic responses in both the HPRT and TK reporter genes, as compared with single-drug exposures (Meng Q et al. [2000a]: Proc Natl Acad Sci USA 97:12667,12671). The purpose of the current study was to characterize the mutational specificity of equimolar mixtures of 100 ,M or 300 ,M AZT + ddI at the HPRT and TK loci of exposed cells vs. unexposed control cells, and to compare the resulting mutational spectra data to those previously found in cells exposed to AZT alone (Sussman H et al. [1999]: Mutat Res 429:249,259; Meng Q et al. [2000b]: Toxicol Sci 54:322,329). Molecular analyses of HPRT mutant clones were performed by reverse transcription,mediated production of cDNA, PCR amplification, and cDNA sequencing to define small DNA alterations, followed by multiplex PCR amplification of genomic DNA to define the fractions of deletion events. TK mutants with complete gene deletions were distinguished by Southern blot analysis. The observed HPRT mutational categories included point mutations, microinsertions/microdeletions, splicing-error mutations, and macrodeletions including partial and complete gene deletions. The only significant difference or shift in the mutational spectra for NRTI-treated cells vs. control cells was the increase in the frequency of complete TK gene deletions following exposures (for 3 days) to 300 ,M AZT,ddI (P = 0.034, chi-square test of homogeneity); however, statistical analyses comparing the observed mutant fraction values (measured mutant frequency × percent of a class of mutation) between control and NRTI-treated cells for each class of mutation showed that the occurrences of complete gene deletions of both HPRT and TK were significantly elevated over background values (0.34 × 10,6 in HPRT and 6.0 × 10,6 in TK) at exposure levels of 100 ,M AZT,ddI (i.e., 1.94 × 10,6 in HPRT and 18.6 × 10,6 in TK) and 300 ,M AZT,ddI (i.e., 5.6 × 10,6 in HPRT and 34.6 × 10,6 in TK) (P < 0.05, Mann,Whitney U -statistic). These treatment-related increases in complete gene deletions were consistent with the spectra data for AZT alone (ibid.) and with the known mode of action of AZT and ddI as DNA chain terminators. In addition, cotreatments of ddI with AZT led to substantial absolute increases in the mutant fraction of other classes of mutations, unlike cells exposed solely to AZT [e.g., the frequency of point mutations among HPRT mutants was significantly increased by 130 and 323% over the background value (4.25 × 10,6) in cells exposed to 100 and 300 ,M AZT,ddI, respectively]. These results indicate that, at the same time that AZT,ddI potentiates therapeutic or prophylactic efficacy, the use of a second NRTI with AZT may confer a greater cancer risk, characterized by a spectrum of mutations that deviates from that produced solely by AZT. Environ. Mol. Mutagen. 39:282,295, 2002. Published 2002 Wiley-Liss, Inc. [source]


Dose-related effects following oral exposure of 2,4-dinitrotoluene on the western fence lizard, Sceloporus occidentalis

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008
Jamie G. Suski
Abstract 2,4-dintitrotoluene (2,4-DNT) is an explosive frequently found in the soil of military installations. Because reptiles can be common on these sites, ecological risk assessments for compounds such as 2,4-DNT could be improved with toxicity data specific to reptiles. Western fence lizards, Sceloporus occidentalis, were used to develop a laboratory toxicity model for reptiles. A hierarchical approach was used; acute to subchronic studies were conducted to provide toxicity data relevant to short- and long-term exposures. First, a modified median lethal dose (LD50) study was conducted on male and female lizards using a stage-wise probit model. The LD50 was 577 mg/kg for female and 380 mg/kg for male lizards. Subsequently, a subacute experiment was conducted to further assess 2,4-DNT toxicity to male lizards and to define exposure levels for a longer term, subchronic study. The subchronic study was conducted for 60 consecutive days; male lizards were exposed to 0, 9, 15, 25, 42, 70 mg/kg/d. Dose-dependent mortality was observed in the three highest dose groups (25, 42, and 70 mg/kg/d); all other animals survived the study duration. Benchmark dose model calculations based on mortality indicated a 5% effect level of 15.8 mg/kg/d. At study termination, a gross necropsy was performed, organ weights were taken, and blood was collected for clinical and hematological analysis. Body weight, kidney weight, food consumption, postdose observations, and blood chemistries all were found to be significantly different from controls at doses above 9 mg/kg/d. Also, preliminary results suggest behavioral observations, and reduced food consumption may be a sensitive indicator of toxicity. The present study indicates Sceloporus occidentalis is suitable for evaluating toxicity of compounds to reptilian species. [source]


In situ reproduction, abundance, and growth of young-of-year and adult largemouth bass in a population exposed to polychlorinated biphenyls

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2004
Dudley W. Reiser
Abstract We conducted a two-year field study (2000,2001) in the Housatonic River, Massachusetts (USA) to determine if we could detect in situ population-level effects on largemouth bass (Micropterus salmoides) exposed to elevated levels of polychlorinated biphenyls (PCBs). Calculated whole-body PCB concentrations in adult bass in 2002 averaged 121 mg/kg (range = 34,556 mg/kg). Polychlorinated biphenyl concentrations in young-of-year (YOY) composites in 2000 and 2002 averaged 28 mg/kg (range = 21,41 mg/kg) and 19 mg/kg (range = 16,24 mg/kg), respectively. Laboratory studies of fish have reported PCB toxicity at exposure levels below and within the range of those found in the Housatonic River. We evaluated five field-derived metrics: reproductive activity, relative abundance of YOY, YOY growth rates, adult growth, and adult condition to determine whether we could detect effects of PCBs in the largemouth bass population. These computed metrics, when compared with data sets assembled for numerous largemouth bass populations in North America, provided no evidence of population-level impairment. Results of this study suggest that PCB tissue concentrations associated with effects in laboratory studies do not necessarily translate to detectable effects on largemouth bass populations in their natural environment. [source]


Organochlorine contaminants in sea turtles: Correlations between whole blood and fat

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2004
Jennifer M. Keller
Abstract Monitoring toxic organochlorine(OC)compounds is an important aspect in wildlife studies, especially in protected species such as sea turtles. The goal of this study was to determine whether blood OC concentrations can predict those in adipose tissue of sea turtles. Blood offers many benefits for monitoring OCs. It can be collected nondestructively from live turtles and can be sampled repeatedly for continuous monitoring. Organochlorine concentrations in blood may better represent the exposure levels of target tissues, but blood concentrations may fluctuate more than those in fatty tissues following recent dietary exposure or lipid mobilization. Paired fat and blood samples were collected from 44 live, juvenile loggerhead sea turtles and 10 juvenile Kemp's ridley sea turtle carcasses. Organochlorines were analyzed using gas chromatography with electron capture detection and mass spectrometry. Lipid-normalized OC concentrations measured in the blood significantly correlated to levels found in the fat samples of both species. This result suggests that sea turtle blood is a suitable alternative to fatty tissues for measuring OCs because blood concentrations reasonably represent those observed in the paired fat samples. However, blood OC concentrations calculated on a wet-mass basis were significantly and inversely correlated to lipid content in the fat samples. Therefore, caution should be used when monitoring spatial or temporal trends, as OC levels may increase in the blood following mobilization of fat stores, such as during long migrations, breeding, or disease events. [source]


Importance of maternal transfer of the photoreactive polycyclic aromatic hydrocarbon fluoranthene from benthic adult bivalves to their pelagic larvae

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2000
Marguerite C. Pelletier
Abstract Laboratory experiments were conducted to determine if maternal transfer of polycyclicaromatichydrocarbons (P AH) from benthic adult bivalves could result in phototoxicity to their pelagic larvae when exposed to ultraviolet light (UV). In these experiments, adult bivalves were exposed to water or sediments amended with the model photoreactive PAH, fluoranthene. Elevated adult fluoranthene tissue concentrations were correlated with embryo concentrations. Embryonic mortality was enhanced by exposure to ultraviolet light when adult tissue fluoranthene levels were greater than 5,000 ,g/g lipid. While the exposure concentrations used in this experimental system were high, ultraviolet light exposure levels were low. Also, some of the PAHs are more potent than the model compound used in this study. These results indicate that maternal transfer of photoactive PAHs from organisms living in contaminated sediments may represent a significant adverse effect to populations of benthic bivalves. [source]


Pesticide residues in the aquatic environment of banana plantation areas in the North Atlantic Zone of Costa Rica

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2000
Luisa E. Castillo
Abstract A study of pesticide residues in surface waters and sediments was undertaken in the Suerte River Basin, Costa Rica, that drains into the Tortuguero conservation area. Samples were collected in streams, packing plants, and the Suerte River. The most frequently measured compounds in surface water samples were the fungicides thiabendazole, propiconazole, and imazalil; the nematicides terbufos and cadusafos; and the insecticide chlorpyrifos. At the conservation area, propiconazole was detected in 43% of the samples at concentrations ranging from 0.05 to 1.0 ,g/L. In 25% of the samples collected at this site, a nematicide (cadusafos, carbofuran, or ethoprophos) was detected (0.06,6.2 ,g/L). According to this study, most of the insecticide-nematicides analyzed pose a risk for acute or chronic toxicity to aquatic organisms based on the exposure levels and toxicity values from the literature. Ametryn, imazalil, and thiabendazole also exceeded the calculated chronic risk ratio. The most frequently detected compounds in sediments were thiabendazole, chlorpyrifos, imazalil, and propiconazole. The occurrence was higher in the packing plants and streams. Pesticides in waters and sediments of Tortuguero conservation area could pose a threat to this wetland and an additional stress to the endangered species that inhabit this area. More information is needed regarding the distribution and stability of pesticides in the lagoon system as well as of the effects of mixtures of low levels of pesticides and their degradation products on representative species of the Tortuguero ecosystem. Meanwhile, all measures to reduce the emissions of pesticides from the banana plantations and the packing plants should be taken. [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]


Riot control agents: pharmacology, toxicology, biochemistry and chemistry,

JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2001
Eugene J. Olajos
Abstract The desired effect of all riot control agents is the temporary disablement of individuals by way of intense irritation of the mucous membranes and skin. Generally, riot control agents can produce acute site-specific toxicity where sensory irritation occurs. Early riot control agents, namely, chloroacetophenone (CN) and chlorodihydrophenarsazine (DM), have been replaced with ,safer' agents such as o -chlorobenzylidene malononitrile (CS) and oleoresin of capsicum (OC). Riot control agents are safe when used as intended: however, the widespread use of riot control agents raises questions and concerns regarding their health effects and safety. A large margin exists between dosages that produce harassment and dosages likely to cause adverse health effects for modern riot control agents such as CS and dibenz[b,f]1 : 4-oxazepine (CR). Yet, despite the low toxicity of modern riot control agents, these compounds are not entirely without risk. The risk of toxicity increases with higher exposure levels and prolonged exposure durations. Ocular, pulmonary and dermal injury may occur on exposure to high levels of these substances, and exposure to riot control agents in enclosed spaces may produce significant toxic effects. Reported deaths are few involving riot control agents, and then only under conditions of prolonged exposure and high concentrations. Recently, concern has focused on the deaths resulting from law enforcement use of OC, a riot control agent generally regarded as safe because it is a natural product. As with other xenobiotics, not enough is known concerning the long-term/chronic effects of riot control agents. Clearly, there is considerable need for additional research to define and delineate the biological and toxicological actions of riot control agents and to illuminate the full health consequences of these compounds as riot control agents. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Histologic evaluation of skin damage after overlapping and nonoverlapping flashlamp pumped pulsed dye laser pulses: A study on normal human skin as a model for port wine stains

LASERS IN SURGERY AND MEDICINE, Issue 2 2001
Petra H.L. Koster MD
Abstract Background and Objective In the treatment of port wine stains (PWS) with the flashlamp pumped pulsed dye laser (FPPDL), no consensus exists about overlapping of pulses. The advantage of overlapping pulses is homogeneous lightening of the PWS; the risk is redundant tissue damage. The aim of this study was to determine the histopathologic effect on human skin of pulsed dye laser pulses with various degrees of overlap, with normal human skin as a model for PWS. Study Design/Materials and Methods Eighteen healthy white volunteers were irradiated with pulsed dye laser pulses with increasing radiant exposure and with different degrees of overlap. Biopsy samples were taken and histologically analysed. Results Overlapping of pulses on normal human skin enhances depth of vascular damage with approximately 30%. Adjacent pulses also show this effect. We found no histologic signs of serious damage to epidermis or dermal connective tissue by using radiant exposure levels of 6,8 J/cm2, regardless of pulse application. Conclusions Reasoning that the mechanism of tissue injury is comparable for normal and PWS skin, we conclude that it is safe to treat PWS with overlapping FPPDL pulses to achieve homogeneous lightening. Lasers Surg. Med. 28:176,181, 2001. © 2001 Wiley-Liss, Inc. [source]


Static Magnetic Fields Affect Capillary Flow of Red Blood Cells in Striated Skin Muscle

MICROCIRCULATION, Issue 1 2008
Gunnar Brix
ABSTRACT Blood flowing in microvessels is one possible site of action of static magnetic fields (SMFs). We evaluated SMF effects on capillary flow of red blood cells (RBCs) in unanesthetized hamsters, using a skinfold chamber technique for intravital fluorescence microscopy. By this approach, capillary RBC velocities (vRBC), capillary diameters (D), arteriolar diameters (Dart), and functional vessel densities (FVD) were measured in striated skin muscle at different magnetic flux densities. Exposure above a threshold level of about 500 mT resulted in a significant (P < 0.001) reduction of vRBC in capillaries as compared to the baseline value. At the maximum field strength of 587 mT, vRBC was reduced by more than 40%. Flow reduction was reversible when the field strength was decreased below the threshold level. In contrast, mean values determined at different exposure levels for the parameters D, Dart, and FVD did not vary by more than 5%. Blood flow through capillary networks is affected by strong SMFs directed perpendicular to the vessels. Since the influence of SMFs on blood flow in microvessels directed parallel to the field as well as on collateral blood supply could not be studied, our findings should be carefully interpreted with respect to the setting of safety guidelines. [source]


Questions regarding the basis of the analyses in study of the relationship of maternal concentrations of dichlorodiphenyl dichloroethylene (DDE) and initiation and duration of breast feeding: extrapolations of organochlorine levels for estimating exposure levels

PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 4 2006
Beth Gladen
First page of article [source]


Noise exposures aboard catcher/processor fishing vessels

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 8 2006
Richard L. Neitzel MS
Abstract Background Commercial fishing workers have extended work shifts and potential for 24 hr exposures to high noise. However, exposures in this industry have not been adequately characterized. Methods Noise exposures aboard two catcher/processors (C/P) were assessed using dosimetry, sound-level mapping, and self-reported activities and hearing protection device (HPD) use. These data were combined to estimate work shift, non-work, and 24 hr overall exposure levels using several metrics. The length of time during which HPDs were worn was also used to calculate the effective protection received by crew members. Results Nearly all workers had work shift and 24 hr noise levels that exceeded the relevant limits. After HPD use was accounted for, half of the 24 hr exposures remained above relevant limits. Non-work-shift noise contributed nothing to 24 hr exposure levels. HPDs reduced the average exposure by about 10 dBA, but not all workers wore them consistently. Conclusions The primary risk of hearing loss aboard the monitored vessels comes from work shift noise. Smaller vessels or vessels with different layouts may present more risk of hearing damage from non-work periods. Additional efforts are needed to increase use of HPDs or implement noise controls. Am. J. Ind. Med. 2006. © 2006 Wiley-Liss, Inc. [source]