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PubMed2006

Food neophobia in the context of a varied diet induced by a weight reduction program in massively obese adolescents.

Previous studies in humans have shown that short to middle-term pre-exposure to multiple foods can reduce the negative response to novel foods (neophobia). In order to explore the effects of a long-term exposure to varied foods on food neophobia, we studied a population of obese adolescents observed in a longitudinal protocol in which the multiple food experiences are induced by a residential weight reduction program (WRP) that encourages the consumption of a wide variety of foods. Seventy-two massively obese adolescents (22 boys) filled the food neophobia scale (FNS, [Pliner, P., & Hobden, K. (1992). Development of a scale to measure the trait of food neophobia in humans. Appetite 19, 105-120]) and an ad hoc food familiarity and liking questionnaire at the beginning and at the end of the program (mean duration: 8.9 months). Their scores were compared to those of a control group of 51 adolescents (14 boys) tested within a similar period. FNS results show a decrease of food neophobia, without significant difference between the control group and the WRP subjects, although only WRP have encountered new foods experiences as attested by the familiarity and liking results. Methodological considerations, concerning the characteristics of the participants, the nature of the multiple food exposure and the food neophobia measurements, will be proposed to explain differences among studies.

Adolescent↗
PubMed1989

Multiple sclerosis and occupational exposure to chemicals: a co-twin control study of a nationwide series of twins.

From the Finnish Twin Cohort (n = 27,100 pairs with known zygosity) all cases of diagnosed multiple sclerosis (MS) were reviewed and those with clinically verified MS were invited for further examinations at the Institute of Occupational Health, Helsinki, with their co-twins. Twenty one cases (19 pairs, of which 17 were discordant) fulfilled the strict criteria of MS. Detailed occupational history showed exposure to a mixture of solvents in six subjects, to lead in one, and to trichloroethylene in one. Of these seven, two monozygotic twins had MS whereas the other five cases were healthy co-twins. These results do not support a causal association between occupational exposure to chemicals and the aetiopathogenesis of MS.

Adult↗
PubMed1989

Epithelial damage in rabbit corneas exposed to CO2 laser radiation.

Corneal injury thresholds are determined for conditions not previously explored for CO2 laser radiation, including multiple-pulse exposures and a systematic investigation of the effect of beam diameter on single-pulse damage thresholds. Multiple-pulse exposures from pulse trains up to 999 pulses, having pulse repetition frequencies between 1 and 100 Hz and individual pulse durations between 10(-3) and 0.5 s, were explored. Damage thresholds are discussed in terms of an approximate critical temperature model, the damage integral model and other empirical correlations. Single-pulse exposures are accurately correlated by an empirical critical temperature model in which the critical temperatures have a weak dependence on exposure duration. However, certain aspects of the single-pulse damage data led us to propose a new thermal damage model that incorporates an endothermic phase transition as the damage mechanism. This physical model accurately correlates single-pulse damage for exposures between 10(-3) and approximately 10 s.

Animals↗
PubMed1983

Multiple isoelectric forms of detergent-solubilized bovine rhodopsin. I. Identity, composition and properties.

Isoelectric focusing was performed on crude bovine rhodopsin (a detergent extract of rod outer segments) and on rhodopsin after purification by adsorption chromatography on calcium phosphate-Celite and affinity chromatography on Con A-Sepharose. The purified unbleached (native) material resolved into three forms of nearly equal amounts having isoelectric points (pI) of 5.19, 5.58 and 6.14. Each form was stable to refocusing. The composition of the three forms as determined by amino acid analysis, phosphate analysis and polyacrylamide gel electrophoresis was the same as that found for unfocused rhodopsin. Each isoelectric form cross-reacted with rabbit antibody to bovine rhodopsin. After photobleaching, one form of opsin was observed, having an isoelectric point of 5.58. While crude rhodopsin showed a single species in the native state (pI of 6.20), multiple forms were revealed after treatment with phospholipase. Purified rhodopsin, after reduction, showed a single major isoelectric point of 6.09 rather than the multiple forms. Exposure of rod outer segments or rhodopsin to antioxidants or rcrude rhodopsin showed a single species in the native state (pI of 6.20), multiple forms were revealed after treatment with phospholipase. Purified rhodopsin, after reduction, showed a single major isoelectric point of 6.09 rather than the multiple forms. Exposure of rod outer segments or rhodopsin to antioxidants or removal of phospholipids led to an alteration in the relative abundance of the multiple isoelectric forms, but not to a change in their isoelectric point.

Amino Acids↗
PubMed2006

The number of genes changing expression after chronic exposure to code division multiple access or frequency DMA radiofrequency radiation does not exceed the false-positive rate.

Experiments with cultured C3H 10T 1/2 cells were performed to determine if exposure to cell phone radiofrequency (RF) radiations induce changes in gene expression. Following a 24 h exposure of 5 W/kg specific adsorption rate, RNA was extracted from the exposed and sham control cells for microarray analysis on Affymetrix U74Av2 Genechips. Cells exposed to 0.68 Gy of X-rays with a 4-h recovery were used as positive controls. The number of gene expression changes induced by RF radiation was not greater than the number of false positives expected based on a sham versus sham comparison. In contrast, the X-irradiated samples showed higher numbers of probe sets changing expression level than in the sham versus sham comparison.

Animals↗
PubMed1993

Chemical interaction: enhancement and inhibition of clastogenicity.

Most environmental exposures involve concurrent or sequential exposure to multiple chemicals in air, water, and food. Interactive effects in carcinogenesis have been described for certain combinations of agents. They are described in terms of enhancement or inhibition of carcinogenesis. Enhancement effects have been documented for cigarette smoking in combination with exposure to asbestos, radon, alcohol, or other exposures. A variety of inhibitors of carcinogenesis have also been described. They are classified into agents preventing formation of carcinogens; blocking agents; and suppressing agents. Assessment of risk from exposure to multiple agents can be derived either from epidemiological studies in relation to actual exposure or from laboratory studies after controlled exposure to different agents. Prediction of how toxic components of mixtures will interact should be based on an understanding of the mechanisms of such interactions. Compounds may interact chemically, yielding new toxic components or causing a change in the biological availability of the existing components or metabolites. In humans, great individual variability in response is to be expected because of genetic heterogeneity or acquired host susceptibility factors. Interaction is thus a key component in the risk assessment process. In this paper, the definition of interaction and the theoretical basis for different types of interaction in cancer causation are reviewed. Epidemiological and experimental studies showing interactive effects of two chemical carcinogens are also presented.

Antimutagenic Agents↗
PubMed1992

Use of human data in quantitative risk assessment of carcinogens: impact on epidemiologic practice and the regulatory process.

Epidemiologic data are increasingly being used to assess cancer risk from chemicals as their value is recognized and as more and better studies become available. Weight-of-evidence approaches are now available for classifying the experimental and epidemiological evidence regarding human carcinogenicity. When the human data are extensive and of good quality, they should be given substantial weight in assessing risk. Both the positive and the negative epidemiologic data should be used in a quantitative risk assessment (QRA), because only then can an unbiased risk assessment be derived. Good-quality epidemiological studies are those with sound methodology, lack of bias, long enough follow-up times to observe a carcinogenic response, adequate exposure information, and dose-response information. Before a lack of carcinogenicity can be inferred, it is essential that the exposures be of substantial duration and intensity, and that the number of exposed persons be reasonably large. Epidemiologists need to give more attention to exposure assessment, because lack of quantitative exposure information is often the limiting factor that prevents the use of epidemiologic data in QRA. Development of methods to estimate historical workplace exposure intensities from surrogate industrial hygiene variables should receive high research priority, since they have the potential to increase the usefulness in QRA of many epidemiologic studies that have limited exposure information. Several frequently used surrogates for exposure measurements have limitations or pitfalls in their use. In particular, the use of "ever/never" exposed has a large potential to produce falsely negative results by means of a "dilution" effect, especially in the common case where the exposure distribution is skewed. Duration of exposure (rather than duration x intensity) may also give misleading results. There is little information to suggest that synergistic exposures to multiple toxicants in an industrial environment are likely to invalidate QRAs, probably because few studies have identified a group of workers with major workplace exposures to multiple carcinogens that cause the same type of cancer. Most of the interactive effects which have been identified to date are between smoking and some occupational carcinogen, so this possibility needs careful evaluation for smoking-related diseases. It is important to evaluate dose-response gradients in a QRA to obtain maximum precision and accuracy in the resulting risk coefficient. The analysis should take into account an appropriate cancer induction period. Various methods to account for cancer induction times are compared; those that incorporate a lag period or model the induction-time distribution are superior to other methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinogens↗
PubMedDate not supplied

Effects of perinatal loratadine exposure on male rat reproductive organ development.

Normal pre- and postnatal male reproductive development and function is dependent upon testicular androgen production and is sensitive to antiandrogenic perturbations. It was of interest to determine if the H(1) histamine antagonist loratadine had the potential to alter androgen-mediated reproductive development in the rat, a sensitive species for detecting antiandrogenic effects. Loratadine was administered orally by gavage to pregnant Sprague-Dawley rats at doses of 4, 12 or 24 mg/kg from gestation day 7 to postnatal day 4, encompassing the period of androgen-dependent male reproductive development. Vehicle control rats received 0.4% aqueous methylcellulose. Dams were allowed to deliver naturally and rear their offspring until postnatal day 21. On postnatal day 21 male offspring were retained for further evaluation of androgen-dependent endpoints and the female offspring were euthanized and their sex confirmed internally. Males were necropsied from postnatal day 72 to 85. Dams administered 24 mg/kg of loratadine exhibited a transient 45% decrement in maternal body weight gain at the initiation of dosing (gestation days 7-9). Mean pup body weight on postnatal days 1 and 4 were approximately 4% lower than controls. No other effects on offspring growth were observed. Anogenital distance on postnatal day 1 was unaffected by loratadine exposure. Loratadine exposure did not induce the retention of nipples in male rats, affect preputial separation, or induce external malformations, including hypospadias. Seminal vesicle and prostate weights were not decreased by loratadine exposure. These data clearly demonstrate that systemic loratadine exposure, in multiples up to 26 times clinical exposure levels, does not exhibit in vivo antiandrogen activity, as evidenced by the absence of alterations or malformations in androgen-dependent reproductive tissues in male rats exposed to loratadine during the critical period of androgen-dependent development.

Androgens↗
PubMed1992

The Workplace Exposure Assessment Expert System (WORKSPERT).

The fundamental principles of industrial hygiene are based upon the recognition, evaluation, and control of workplace hazards. Occupational safety and health professionals (e.g., industrial hygienists) perform this task by assessing numerous complex factors. In many situations industrial hygienists are not available; therefore, an expert system has been developed to assist the performance of workplace exposure assessments (WEAs). The Workplace Exposure Assessment Expert System (WORKSPERT) evaluates various hazardous substances, workplace conditions, and worker exposures for designated homogeneous exposure groups (HEGs). The three major components of WORKSPERT (i.e., substance, workplace, and exposure factors) are described by 27 multiple attribute variables. An air monitoring program (AMP) may be recommended for each HEG based upon the WEA. The AMP provides recommendations for an appropriate sampling strategy, sampling duration, multiple substance exposures, and number of samples to be obtained in the future. The use of WORKSPERT or other expert systems should never supersede the judgment of occupational safety and health professionals. However, WORKSPERT can be a valuable tool when used by knowledgeable, qualified technical professionals (e.g., safety and health specialists, chemists, engineers, and toxicologists) who understand the specific substance, workplace, and exposure factors for designated HEGs. WORKSPERT allows these people to benefit from the expertise of an industrial hygienist by performing systematic evaluations and obtaining recommendations for corrective actions or an AMP. The use of WORKSPERT to perform WEAs promotes the protection of workers from hazardous substances and assists compliance with occupational safety and health regulations. It also facilitates the communication of substance hazards, workplace controls, and worker exposures in a succinct manner.

Air Pollutants, Occupational↗
PubMed2005

Exposures to refractory ceramic fibers in manufacturing and related operations: a 10-year update.

Refractory ceramic fiber (RCF) is a man-made vitreous fiber used for its insulating properties. Since 1987, the work environment of approximately 800 persons employed in fiber manufacture or production operations directly related to manufacturing has been monitored to evaluate exposure levels. Samples were collected quarterly from the breathing zones of randomly selected workers. The measurements from those working in areas of similar activities and exposure controls (dust zones or homogeneous exposure groups) were used to calculate a mean exposure during identified time periods. Persons who spent all of their work time in one zone/group were assigned this mean exposure; those with responsibilities in more than one area were assigned an exposure based on a time-weighted formula. A total of 3213 measurements were used to estimate exposure for 130 job titles; because of the mobile jobs, many samples contribute to the estimates of exposure for multiple job titles. The majority of exposure estimates (53%) have remained stable over the operational history of the plant reported here. For 32 job titles (25%) exposures have decreased, and for 28 job titles (22%) exposures have increased. Of the 122 job titles active in 2001, 97 (79%) exposures were estimated to be at 0.25 f/cc or lower; 8 (7%) had an exposure exceeding 0.5 f/cc (range 0.51-0.80) and 17 (14%) of these exposure estimates were in the range of > 0.25 f/cc to 0.5 f/cc. The continuing program to measure exposure supports a respiratory health surveillance program in these facilities.

Adult↗
PubMed1998

Retrospective exposure assessment for a cohort study into respiratory effects of acid anhydrides.

OBJECTIVES: To estimate past exposure to phthalic (PA), trimellitic (TMA) and maleic anhydride (MA) in three alkyd resin and one cushioned flooring factory to estimate exposure-response relations in a retrospective cohort study. METHODS: Personal exposure measurements were carried out in 1992 and quantitative and qualitative information on past exposure and production processes were collected. Job titles were ranked by decreasing exposure and amalgamated into job categories and exposure groups. Multiplication factors for back calculating past exposure levels were estimated with past exposure data, or if no such data were available these factors were estimated by a panel of occupational hygienists. Exposure levels were back calculated starting with the exposure levels in 1992. RESULTS: High exposures to PA were estimated to have occurred among workers operating the PA melting pots in factory 1 (estimated exposure in 1960-9 was 2480 micrograms.m-3). Highest concentrations of TMA were estimated to have occurred among the ink mixers in factory 2 from 1979 to 1986 (554 micrograms.m-3). Exposure in most other job titles was thought to be fairly constant over time for PA, TMA, and MA. CONCLUSIONS: Exposure to acid anhydride at these factories has fallen during the period covered by the study. However, it is estimated that in only one job in factory 2 did past exposure to acid anhydride exceed the current occupational exposure standard. Accuracy of the estimated exposure is limited by a paucity of reliable past exposure data.

Anhydrides↗
PubMed2005

Air pollution exposure assessment for epidemiologic studies of pregnant women and children: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research.

The National Children's Study is considering a wide spectrum of airborne pollutants that are hypothesized to potentially influence pregnancy outcomes, neurodevelopment, asthma, atopy, immune development, obesity, and pubertal development. In this article we summarize six applicable exposure assessment lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research that may enhance the National Children's Study: a) Selecting individual study subjects with a wide range of pollution exposure profiles maximizes spatial-scale exposure contrasts for key pollutants of study interest. b) In studies with large sample sizes, long duration, and diverse outcomes and exposures, exposure assessment efforts should rely on modeling to provide estimates for the entire cohort, supported by subject-derived questionnaire data. c) Assessment of some exposures of interest requires individual measurements of exposures using snapshots of personal and microenvironmental exposures over short periods and/or in selected microenvironments. d) Understanding issues of spatial-temporal correlations of air pollutants, the surrogacy of specific pollutants for components of the complex mixture, and the exposure misclassification inherent in exposure estimates is critical in analysis and interpretation. e) "Usual" temporal, spatial, and physical patterns of activity can be used as modifiers of the exposure/outcome relationships. f) Biomarkers of exposure are useful for evaluation of specific exposures that have multiple routes of exposure. If these lessons are applied, the National Children's Study offers a unique opportunity to assess the adverse effects of air pollution on interrelated health outcomes during the critical early life period.

Air Pollutants↗
PubMed1991

Back disorders and nonneutral trunk postures of automobile assembly workers.

A case-referent study was conducted in an automobile assembly plant to evaluate the health effect of trunk postures, such as bending and twisting, that deviate from anatomically neutral. Cases of back disorders were all those of workers who reported back pain to the medical department in a ten-month period and met the severity criteria of an interview. The referents were randomly selected workers free of back pain according to medical department records, an interview, and an examination. For each of the final 95 cases and 124 referents, the job was analyzed for postural and lifting requirements with a video recording and software analysis system by analysts blinded to the case/referent status. Back disorders were associated with mild trunk flexion [odds ratio (OR) 4.9, 95% confidence interval (95% CI) 1.4-17.4], severe trunk flexion (OR 5.7, 95% CI 1.6-20.4), and trunk twist or lateral bend (OR 5.9, 95% CI 1.6-21.4). The risk increased with exposure to multiple postures and increasing duration of exposure.

Adult↗
PubMedDate not supplied

From a theoretical framework of human exposure and dose assessment to computational system implementation: the Modeling ENvironment for TOtal Risk Studies (MENTOR).

Georgopoulos and Lioy (1994) presented a theoretical framework for exposure analysis, incorporating multiple levels of empirical and mechanistic information while characterizing/reducing uncertainties. The present review summarizes efforts towards implementing that framework, through the development of a mechanistic source-to-dose Modeling ENvironment for TOtal Risks studies (MENTOR), a computational toolbox that provides various modeling and data analysis tools to facilitate assessment of cumulative and aggregate (multipathway) exposures to contaminant mixtures. MENTOR adopts a "Person Oriented Modeling" (POM) approach that can be applied to either specific individuals or to populations/subpopulations of interest; the latter is accomplished by defining samples of "virtual" individuals that statistically reproduce the physiological, demographic, etc., attributes of the populations studied. MENTOR implementations currently incorporate and expand USEPA's SHEDS (Stochastic Human Exposure and Dose Simulation) approach and consider multiple exposure routes (inhalation, food, drinking water intake; non-dietary ingestion; dermal absorption). Typically, simulations involve: (1) characterizing background levels of contaminants by combining model predictions and measurement studies; (2) characterizing multimedia levels and temporal profiles of contaminants in various residential and occupational microenvironments; (3) selecting sample populations that statistically reproduce essential demographics (age, gender, race, occupation, education) of relevant population units (e.g., census tracts); (4) developing activity event sequences for each member of the sample by matching attributes to entries of USEPA's Consolidated Human Activity Database (CHAD); (5) calculating intake rates for the sample population members, reflecting physiological attributes and activities pursued; (6) combining intake rates from multiple routes to assess exposures; (7) estimating target tissue doses with physiologically based dosimetry/toxicokinetic modeling.

Complex Mixtures↗
PubMed2003

Application of toxicogenomic analysis to risk assessment of delayed long-term effects of multiple chemicals, including endocrine disruptors in human fetuses.

Our previous studies analyzing umbilical cords show that human fetuses in Japan are exposed to multiple chemicals. Because of these findings, we believe it is necessary to establish a new strategy for examining the possible delayed long-term effects caused by prenatal exposure to multiple chemical combinations and evaluating the health risk to human fetuses. In this commentary we describe our attempts to apply toxicogenomic analysis of umbilical cords, using DNA microarray for future risk assessment. Because the umbilical cord is part of the fetal tissue, it is possible to estimate the effects of chemicals on the fetus by analyzing alteration of the gene expression. This type of toxicogenomic analysis could be a powerful and effective tool for developing a new risk assessment strategy to help investigators understand and possibly prevent long-term effects caused by fetal exposure to multiple chemicals. Worldwide cooperation is needed to establish a new stragegy for risk assessment using toxicogenomic analysis that focuses on the human fetus.

Animals↗
PubMed1990

Worksite behavioral research. Results, sensitive methods, test batteries and the transition from laboratory data to human health.

Ample evidence demonstrates that many chemicals, at some concentration, affect the nervous system. Disastrous incidents resulting from food adulteration, medical experiments and pharmaceutical errors, and industrial and environmental exposures warn of the serious potential for neurotoxicants to affect human health. This article identifies the approximately 185 epidemiological behavioral neurotoxicology studies published through 1989 of extended workplace exposures to chemicals. Approximately 250 different tests have been administered to exposed workers in primarily cross sectional studies, and statistically significant decrements were reported in 43% of the approximately 1100 test/population administrations (virtually all 185 studies employed several of the 250 tests). In this research, 28 different chemicals as well as multiple chemical exposures have been studied. The most extensive findings are seen in research on carbon disulfide, lead, mercury, and multiple solvent exposures, although three or more independent studies also have been reported on workers exposed to styrene and organophosphates. Analyzing the consistent findings in these studies, they reveal a broad spectrum of cognitive, motor, and affective or personality changes. The most frequently reported functional deficits are in tests of intelligence, memory, spatial relations, coordination, and speed plus coordination. Individual behavioral measurement methods and significant test batteries that have been employed to assess changes in human nervous system functions to determine the degree of risk posed by new and established chemicals are described; two of those human behavioral test batteries are predicted to dominate research at the onset of the 1990's. There is a lack of parallelism between the human test methods found in these batteries and the US Environmental Protection Protection Agency (EPA) and Food and Drug Agency (FDA) guideline methods for pre-production screening of chemicals and food additives in animals, and it appears unlikely that the widely employed human and animal behavioral test batteries, as currently evaluated, could identify disease complexes newly suspected of having a chemical etiology.

Animals↗
PubMed2006

Estimating blood needs for very-low-birth-weight infants.

BACKGROUND: Red blood cell (RBC) transfusions are crucial for the care of very-low-birth-weight (VLBW) infants. These infants frequently require multiple, small-volume RBC transfusions, with potential exposure to multiple donors. Optimal protocols provide dedicated RBC units to reduce exposures and avoid RBC wastage. STUDY DESIGN AND METHODS: This study was a retrospective, single-institution review of RBC transfusions in VLBW infants. The RBC volume transfused during the entire hospitalization (VTH) and that transfused at 35 days were determined for all infants, 401 to 1250 g at birth, admitted to a Level III neonatal intensive care unit from January 1, 2000, through December 31, 2002. Multivariable models identified perinatal factors associated with volume transfused. RESULTS: The 640-infant cohort had a median birth weight (BW) of 818 g and gestational age (GA) of 26 weeks. Most infants (546 or 85%) required at least one RBC transfusion. Median number of RBC transfusions was 3 (range, 0-30) and median volume transfused was 82 mL (range, 9-737 mL). Of 328 infants who received all transfusions within a 35-day period, only 5 (1.5%) required at least 200 mL. VTH was inversely related to BW and GA. Multivariable models identified BW, GA, age at first transfusion, and use of inotropes as variables associated with higher volume transfused. CONCLUSION: Few VLBW infants use an entire RBC unit. One dedicated unit shared by two or more infants should meet their transfusion needs. GA, BW, and markers of illness severity predict increased RBC volume requirements.

Body Weight↗