Combining In Vivo Data with In Silico Predictions for Modeling Hepatic Steatosis by Using Stratified Bagging and Conformal Prediction.

Hepatic steatosis (fatty liver) is a severe liver disease induced by the excessive accumulation of fatty acids in hepatocytes. In this study, we developed reliable in silico models for predicting hepatic steatosis on the basis of an in vivo data set of 1041 compounds measured in rodent studies with repeated oral exposure. The imbalanced nature of the data set (1:8, with the "steatotic" compounds belonging to the minority class) required the use of meta-classifiers-bagging with stratified under-sampling and Mondrian conformal prediction-on top of the base classifier random forest. One major goal was the investigation of the influence of different descriptor combinations on model performance (tested by predicting an external validation set): physicochemical descriptors (RDKit), ToxPrint features, as well as predictions from in silico nuclear receptor and transporter models. All models based upon descriptor combinations including physicochemical features led to reasonable balanced accuracies (BAs between 0.65 and 0.69 for the respective models). Combining physicochemical features with transporter predictions and further with ToxPrint features gave the best performing model (BAs up to 0.7 and efficiencies of 0.82). Whereas both meta-classifiers proved useful for this highly imbalanced toxicity data set, the conformal prediction framework also guarantees the error level and thus might be favored for future studies in the field of predictive toxicology.

Alteraciones de sensibilidad al contraste y estereopsis en trabajadores expuestos a hidrocarburos aromáticos / Alterations of sensitivity to contrast and stereopsis in workers exposed to aromatic hydrocarbons

Objetivos: Los hidrocarburos aromáticos son compuestos que pueden afectar el Sistema Nervioso Central (SNC), provocar neurotoxicidad y asociarse con alteraciones de la función visual. Objetivo general: Establecer la frecuencia de alteraciones en sensibilidad al contraste (SC) y estereopsis, en un grupo de trabajadores expuestos y un grupo no expuestos a hidrocarburos aromáticos. Materiales y métodos: estudio analítico de corte transversal. Muestra: grupo control 20 sujetos, edad media 25 años; grupo expuesto 20 sujetos, edad media 33,4 años. Se realizó valoración optométrica, se evaluaron las vías visuales bajas a través de una prueba de SC con el test FACT (Functional Acuity Contrast Test) y las vías visuales intermedias por la estereopsis con el test Frisby. Resultados: Existe diferencia clínica y estadísticamente significativa para los valores de las frecuencias espaciales de 3.0 cpd, 6.0 cpd y 12.0 cpd, del grupo control comparado con el grupo expuesto, al igual que en la estereopsis fina

Objectives: Aromatic hydrocarbons are compounds that can affect the Central Nervous System (CNS), cause neurotoxicity and be associated with alterations in visual function. Course objective: To establish the frequency of alterations in contrast sensitivity (SC) and stereopsis, in a group of exposed workers and a group not exposed to aromatic hydrocarbons. Materials and methods: cross-sectional analytical study. Sample: control group 20 subjects, average age 25; exposed group 20 subjects, mid age 33.4. An optometric assessment was performed; the low visual pathways were evaluated through an SC test with the FACT test (Functional Acuity Contrast Test) and the intermediate visual pathways by stereopsis with the Frisby test. Results: There is a clinically and statistically significant difference for the values of the spatial frequencies of 3.0 cpd, 6.0 cpd and 12.0 cpd, of the control group compared to the exposed group, as in the fine stereopsis

Blood BTEX levels and neurologic symptoms in Gulf states residents.

BACKGROUND: The chemicals benzene, toluene, ethylbenzene, and xylenes (BTEX) are neuroactive. Exposures often co-occur because they share common sources. We examined neurologic effects of environmental BTEX exposure among U.S. Gulf coast residents taking into account concomitant exposures. METHODS: We measured blood concentrations of BTEX in 690 Gulf state residents. Neurologic symptoms were ascertained via telephone interview. We used log-binomial regression to estimate associations between blood BTEX levels and self-reported neurologic symptoms independently for the presence of any neurologic, central (CNS), or peripheral nervous system (PNS) symptoms. We estimated associations in single chemical models mutually adjusted for co-occurring BTEX and used weighted quantile sum regression to model associations between the combined BTEX mixture and neurologic symptoms. RESULTS: Half (49%) of participants reported at least one neurologic symptom. Each BTEX chemical was associated with increased CNS and PNS symptoms in single-chemical models comparing the highest to lowest quartile of exposure. After adjusting for coexposures, benzene was associated with CNS symptoms among all participants (PR = 2.13, 95% CI: 1.27, 3.57) and among nonsmokers (PR = 2.30, 95% CI: 1.35, 3.91). After adjusting for coexposures, associations with toluene were apparent only for reporting multiple PNS symptoms (PR = 2.00, 95% CI: 0.96, 4.16). In mixture analyses, a one-quartile increase in BTEX exposure was associated with neurologic symptoms (OR = 1.47, 95% CI: 1.11, 1.98). The weighted quantile sum index weighted benzene most heavily, which was consistent with single chemical analyses. CONCLUSIONS: Increasing blood benzene concentration was associated with increased prevalence of CNS symptoms. In this sample, BTEX-associated neurologic effects are likely driven by exposure to benzene and, to a lesser extent, toluene.

An overview of health hazards of volatile organic compounds regulated as indoor air pollutants.

Indoor air quality (IAQ) standards and guidelines for volatile organic compounds (VOCs) have been stipulated by various national and international agencies. The main purpose of this paper is to establish an overview of indoor VOCs regarding their impacts on human health. Herein, 13 VOCs were designated as indoor air pollutants (IAPs) in the IAQ standards and guidelines. They were further grouped into four types: nonchlorinated aromatic compounds, chlorinated aromatic compounds, chlorinated aliphatic compounds and aldehydes. For this purpose, the present study discusses the criteria for designating VOCs, and summarizes their main sources in indoor environments. Because the occupational exposure limit (OEL) in workplaces has often used as a preliminary basis for establishing acceptable health-based IAQ guidelines in buildings and residences, this paper thus reviews the OEL values, especially in the American Conference of Governmental Industrial Hygienists (ACGIH)-threshold limit value (TLV). In addition, this paper also reviews the information about the classification of carcinogenicity in human by the international agencies for these VOCs. It shows that human tissues, including kidney, liver, leukemia, nasal cavity, paranasal sinus, liver and bile duct, could be more involved in the development of cancers or tumors when people are exposed to these VOCs through inhalation route in buildings over a long period of time.

Aromatic hydrocarbon receptor provides a link between smoking and rheumatoid arthritis in peripheral blood mononuclear cells.

OBJECTIVES: Epidemiology shows that smoking plays a central role in rheumatoid arthritis (RA). The aim of this study was to evaluate the potential relationship between smoking, aromatic hydrocarbon receptor (AHR) and RA susceptibility. METHODS: We performed a hospital-based, case-control study of patients with RA and healthy controls. Expressions of AHR, cytochrome P4501A1(CYP1A1), aromatic hydrocarbon receptor repressor (AHRR) genes were assessed in peripheral blood mononuclear cells (PBMCs) and cultured cells using real-time PCR. The response of PBMCs to the AHR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cigarette smoke extract (CSE) were cultured in vitro. RESULTS: AHR and its downstream gene expressions were demonstrated in smoking rheumatoid PBMCs and non-smoking patients with significantly higher expression in smoking patients. The observation was consistent with the sensitivity of RA PBMCs to TCDD and CSE stimulation demonstrated in vitro. CONCLUSIONS: Our study shows that smoking may be involved in the pathogenesis of RA by the AHR pathway.

The association of HLA B*15:02 allele and Stevens-Johnson syndrome/toxic epidermal necrolysis induced by aromatic anticonvulsant drugs in a South Indian population.

BACKGROUND: The presence of HLA-B*15:02 allele is considered a risk factor for development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in patients taking aromatic anticonvulsant drugs like carbamazepine and phenytoin. The genetic association is ethnicity specific. Testing for HLA-B*15:02 allele is suggested as a prerequisite before starting carbamazepine in certain ethnic groups. There are only a few/no studies from south India on HLA association of SJS/TEN. AIMS: To identify any association between HLA-B*15:02 allele and SJS/TEN induced by carbamazepine/phenytoin among native population. METHODS (INCLUDING SETTINGS, DESIGN, AND STATISTICAL ANALYSIS USED): A case-control study done in a tertiary care center at Kottayam in Kerala state of south India. Cases were 12 native patients who developed SJS/TEN owing to aromatic anticonvulsant drugs (phenytoin - 8; carbamazepine - 4), and controls were 11 persons tolerant to these drugs from unrelated families of the same ethnic group. HLA-B typing was done by PCR SSP method. RESULTS: There was only one HLA-B*15:02 carrier among cases and controls. He/she had SJS/TEN induced by carbamazepine. CONCLUSIONS: Association of HLA-B*15:02 with phenytoin-induced SJS/TEN is rare in the population studied. The one limitation of the study was the small sample size.

[THE BIOCHEMICAL AND PATHOPHYSIOLOGICAL MARKERS OF CHEMICAL EFFECT ON ORGANISM, THEIR INFORMATIVENESS AND DIAGNOSTIC SIGNIFICANCE].

The sampling of study included 185 examined workers. Out of them 90 work at "Opitnii zavod Neftekhim" (67 females and 23 males) and 95--at "Kaustik" (64 females and 31 males) from various workshops of the given enterprises. To determine biochemical indicators samples of blood, saliva and urine were collected. The study was carried out in concordance with ethic principles of the Helsinki world medical association declaration, 2008 ed. with receiving written consent of patient to participate in study.

Urinary polyaromatic hydrocarbons are associated with adult celiac disease and kidney stones: USA NHANES, 2011-2012.

Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons (PAH) were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols, and pesticides. Therefore, it was aimed to study the relationships of urinary PAH and adult digestive conditions using a large human sample in a national and population-based study in recent years. Data was retrieved from the US National Health and Nutrition Examination Surveys, 2011-2012 including demographics, self-reported health conditions, and urinary PAH. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling, and population attributable risk (PAR) estimation. Of 5560 American adults aged 20-80 and included in the statistical analysis, urinary 4-hydroxyphenanthrene was significantly associated with celiac disease (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.14-2.26, P = 0.009). In addition, urinary 2-hydroxyfluorene (OR 1.35, 95% CI 1.02-1.78, P = 0.038), 3-hydroxyfluorene (OR 1.35, 95% CI 1.07-1.70, P = 0.015), 1-hydroxyphenanthrene (OR 1.48, 95% CI 1.08-2.03, P = 0.017), 1-hydroxypyrene (OR 1.36, 95% CI 1.05-1.77, P = 0.023), and 2-hydroxynapthalene (OR 1.25, 95% CI 1.00-1.58, P = 0.054) were significantly associated with kidney stones, although not necessarily failing kidney. There were no statistically significant associations observed in the relationship of urinary PAH and liver problems, although higher levels of PAHs were observed. Urinary PAHs are associated with adult digestive conditions, although the causality cannot be established. From the research perspective, longitudinal monitoring from observational studies and experimental research understanding mechanism would be suggested. Regulation of minimizing PAHs exposure might need to be considered in future health and environmental policies.

[Characteristics of regulatory system in children exposed to the environmental chemical factors].

In children residing in areas with a high content of a number of aromatic hydrocarbons in ambient air and organochlorine compounds in drinking water there were studied the blood levels of these compounds, as well as the assessment of the indices of the immune and neuroendocrine systems was performed. The higher blood content of phenol and formaldehyde has been established and there was identified an array of organochlorine and aromatic compounds not detected in the control group children. In the blood of the children of a study group there was found an imbalance of indices of cellular components of innate and adaptive immunity, pro- and anti-inflammatory cytokines, as well as increased concentrations of free thyroxine and serotonin in the blood serum, which indicates to a change in the functions of regulatory systems in children exposed to organochlorine and aromatic compounds.

Optimal design for the precise estimation of an interaction threshold: the impact of exposure to a mixture of 18 polyhalogenated aromatic hydrocarbons.

Traditional additivity models provide little flexibility in modeling the dose-response relationships of the single agents in a mixture. While the flexible single chemical required (FSCR) methods allow greater flexibility, its implicit nature is an obstacle in the formation of the parameter covariance matrix, which forms the basis for many statistical optimality design criteria. The goal of this effort is to develop a method for constructing the parameter covariance matrix for the FSCR models, so that (local) alphabetic optimality criteria can be applied. Data from Crofton et al. are provided as motivation; in an experiment designed to determine the effect of 18 polyhalogenated aromatic hydrocarbons on serum total thyroxine (T(4)), the interaction among the chemicals was statistically significant. Gennings et al. fit the FSCR interaction threshold model to the data. The resulting estimate of the interaction threshold was positive and within the observed dose region, providing evidence of a dose-dependent interaction. However, the corresponding likelihood-ratio-based confidence interval was wide and included zero. In order to more precisely estimate the location of the interaction threshold, supplemental data are required. Using the available data as the first stage, the Ds-optimal second-stage design criterion was applied to minimize the variance of the hypothesized interaction threshold. Practical concerns associated with the resulting design are discussed and addressed using the penalized optimality criterion. Results demonstrate that the penalized Ds-optimal second-stage design can be used to more precisely define the interaction threshold while maintaining the characteristics deemed important in practice.

Maternal occupational exposure to organic solvents during early pregnancy and risks of neural tube defects and orofacial clefts.

OBJECTIVES: Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, the authors examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs). METHODS: Cases of NTDs (anencephaly, spina bifida and encephalocoele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in eight states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. ORs and 95% CIs for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking. RESULTS: The prevalence of exposure to any solvent among mothers of NTD cases (n = 511), OFC cases (n = 1163) and controls (n = 2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR = 1.96, CI 1.34 to 2.87), especially spina bifida (OR = 2.26, CI 1.44 to 3.53). No solvent class was strongly associated with OFCs in these data. CONCLUSIONS: The findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.

A review of epidemiological studies on neuropsychological effects of air pollution.

The aim of the present review is to provide an update of the epidemiological evidence of the effects of air pollution on neuropsychological development and impairment, as well as of the evidence on individual susceptibility to these effects. Animal studies have shown deposition of ultrafine particles containing metals in olfactory bulb and frontal cortical and subcortical areas, and overexpression of inflammatory responses, white matter lesions and vascular pathology in these areas that could be the basis for functional and structural brain effects. Several observational studies in the general population have observed cognitive deficits and behavioural impairment in children and the elderly. These effects, however, are not conclusive given the limited number of studies, their small size and their methodological constraints.

Utilización de compuestos orgánicos volátiles (COV) como disolventes en empresas españolas / Use of volatile organic compounds (VO Cs) as solvents in Spanish companies

Objetivo. Trabajadores de prácticamente todos los sectores de actividad están expuestos a compuestos orgánicos volátiles(COV), sustancias que pueden ocasionar graves daños sobre la salud y el medio ambiente. El objetivo de este trabajo esdescribir el uso de COV en empresas españolas, incluyendo información sobre su toxicidad, principales usos y medidas preventivasaplicadas para su utilización.Métodos. Se describen los datos obtenidos en 156 empresas de diferentes sectores y características participantes en elproyecto denominado “Prevención y control de sustancias disolventes peligrosas”, desarrollado por el Instituto Sindical deTrabajo, Ambiente y Salud (ISTAS) en colaboración con Comisiones Obreras. En cada una de estas empresas se obtuvo informaciónsobre el uso de COV en los procesos productivos a través de la observación, la consulta de fichas de datos de seguridad(FDS) y de entrevistas con delegados y técnicos de prevención.Resultados. Los COV utilizados con mayor frecuencia son hidrocarburos aromáticos (xileno, tolueno y etilbenceno). Losusos más frecuentes son recubrimiento y limpieza de superficies y en adhesivos. Se identificó la utilización de 132 COV diferentes,un 40% de los mismos con efectos tóxicos conocidos sobre la salud. La mayoría se utilizan de forma habitual en lasempresas. El 43% de las FDS localizadas para estos productos presentan errores, siendo mayor el número de errores conformedisminuye el tamaño de la empresa (p=0,031). La medida preventiva más utilizada son los equipos de protección individual.Conclusiones. Los resultados muestran la necesidad de reforzar la aplicación de la normativa en las empresas, así comode desarrollar actividades preventivas específicas sobre COV, en particular la sustitución de los productos más tóxicos(AU)

Objective. Workers are exposed to volatile organic compounds (VOCs) in almost every segment of industry. SeveralVOCs can cause significant adverse effects on health and the environment. The aim of this paper was to describe the uses ofVOCs in Spanish companies, including information on their toxicity, main uses and on the preventive measures adopted.Methods. The data were obtained from 156 companies in different sectors participating in the project “Prevention andcontrol of dangerous solvents”, carried out by the Work, Environment and Health Union Institute (ISTAS) in collaborationwith the trade union Comisiones Obreras. Information on the VOCs used in production processes was obtained throughobservation, consultation of material safety data sheets (MSDS) and interviews with safety representatives and health andsafety professionals.Results. The most frequently used VOCs were aromatic hydrocarbons (xylene, toluene and ethylbenzene) and the mostcommon tasks involve surface cleaning, coating processes and adhesive compounds. The use of 132 different VOCs was identified,40% of which have known toxic effects, and most of these products are commonly used by companies. Forty-three percent of the MSDS reviewed contained incorrect information, and the number of errors increased as the size of the companiesdecreased (p=0.031). Preventive measures mostly centered on the use of personal protective equipment.Conclusions. These data underscore the need for greater enforcement of current legislation in Spain, as well as for thedevelopment of specific preventive interventions, mostly substitution of toxic VOCs with safer alternatives(AU)

Intake of heterocyclic aromatic amines and the risk of prostate cancer in the EPIC-Heidelberg cohort.

BACKGROUND: Heterocyclic amines (HCA) are positively associated with prostate cancer risk in animal models. Because of mostly inconsistent results of epidemiological studies, we examined the association between intake of HCA and prostate cancer risk. METHODS: In the EPIC-Heidelberg cohort, detailed information on diet, anthropometry, and lifestyle was assessed between 1994 and 1998. Dietary HCA intake was estimated using information on meat consumption, cooking methods, and preferred degree of browning. During 104,195 person-years of follow-up, 337 incident cases of prostate cancer (123 advanced cases) were identified among 9,578 men with valid dietary information. Multivariate Cox proportional hazards regression was used to examine the association between intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and prostate cancer. RESULTS: Men in the highest quartiles of PhIP, MeIQx, and DiMeIQx intake, respectively, had no increased risk of prostate cancer compared with men in the lowest quartiles (HR = 0.89, 95% CI 0.66-1.22 [PhIP]; 1.06, 0.77-1.45 [MeIQx]; 0.98, 0.72-1.34 [DiMeIQx]). There were no associations between HCA intake and advanced prostate cancer or between high consumption of strongly browned meat and prostate cancer. DISCUSSION: Our data do not support the hypothesis that HCA intake as consumed in a regular diet is a risk factor for prostate cancer.

[Assessment of exposure to cancerogenic aromatic hydrocarbon during controlled-access highways management activities]. / Valutazione dell'esposizione ad idrocarburi aromatici cancerogeni nell'attività di gestione autostradale.

The purpose of this study was an integrated assessment of exposure to benzene and Polycyclic Aromatic Hydrocarbons (PAH) in 29 workers employed to manage a controlled-access highways. A campaign was performed in summertime by environmental monitoring (active and passive airborne personal sampler), as well as by biological monitoring (urine samples of the beginning and of the end of daily shift, baseline after two days of vacation). The measured environmental levels did not differ from background environmental concentrations found in a metropolitan area (i.e. benzo[a]pyrene < 1 ng/m3; benzene < 5 mcg/m3), and the results of biological monitoring were in agreement and were compatible with extra-professional habits of the investigated subjects (1-hydroxipyrene 50-990 ng/g creatinine; unmetabolized benzene 15-2010 ng/I; t-t muconic acid < 4-222 mcg/g creatinine).

[Biomonitoring serum aromatic hydrocarbons in workers engaged in oil extraction industry].

Federal Research Center of Medical and preventive technologies of risk management to public health: in this paper, we present the results of aromatic hydrocarbons biomonitoring in blood of oil-producing industry workers.

Polyhalogenated aromatic hydrocarbons and metabolites: Relation to circulating thyroid hormone and retinol in nestling bald eagles (Haliaeetus leucocephalus).

Polyhalogenated aromatic hydrocarbons are global contaminants that are often considered to be endocrine disruptors and include 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-DDE), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). The present study examined these compounds and their hydroxylated metabolites or analogues and relationships with circulating thyroid hormones and retinols in plasma from nestling and adult bald eagles in British Columbia, Canada, and California, USA. We also compared our results with published data. Thyroxine (T4) decreased with summation operatorPCB and CB153 in nestling bald eagles, which was congruent with results from nine of 14 other published avian laboratory and field studies. Free thyroid hormone levels also decreased with CB-153 and hydroxylated PCBs (OH-PCBs). Retinol increased with CB118 and CB180 in nestling eagles, decreased with OH-PCBs in a subset of nestlings, and decreased in 7 of 12 PCB published studies. Thyroxine decreased with p,p'-DDE for nestlings and with data reported in one of five other published studies. In our samples, plasma retinol, triiodothyronine (T3), and T4 were independent of summation operatorPBDEs, whereas summation operatorOH-PBDEs were weakly but significantly correlated with increases in T3 and retinol. Adult bald eagles showed no relationship between contaminants and thyroid hormones, which is consistent with other studies of long-lived birds, perhaps because adult birds have time to adjust to contaminant levels. Measurement of circulating thyroid hormones appears to be a more useful biomarker than retinols, given the more consistent response of T4 to PCBs here and reported in the literature. We conclude that current environmental exposures to PCBs in British Columbia and in southern California are associated with significant decreases in T4, suggesting a potential negative effect on the endocrine system of nestling bald eagles.

A novel total petroleum hydrocarbon fractionation strategy for human health risk assessment for petroleum hydrocarbon-contaminated site management.

Human health risk assessments for petroleum, oil, and lubricant (POL)-contaminated sites are more complicated than for sites contaminated by single compounds due to the complex composition and various analytical methods associated with total petroleum hydrocarbons (TPH). Although several TPH fractionation methods are commonly used, including that of the TPH Criteria Working Group (TPHCWG), an efficient and economical human health risk assessment method is not yet available. To address this concern, a new modified fractionation strategy is recommended in this study, which resolves the problems of the current TPH fractionation methods while retaining reliability in the results. For the purpose of this study, the distribution characteristics of the 13 TPHCWG fractions were examined, and human health risk assessments for the POL-contaminated sites were performed. The results show that aliphatic EC8-16 and aromatic EC10-21 among the 13 TPH fractions are major contributors to human health risks along all exposure routes, making up approximately 96% of the hazard index (HI) of the TPH fractions, on average. Therefore, it is reasonable to concentrate on aliphatic EC8-16 and aromatic EC10-21 fractions, rather than to study all of the TPH fractions, in evaluating human health risk for TPH-contaminated sites.

[State of adenylic system in experimental animals exposed to chlorinated and aromatic hydrocarbons, organic solvents].

The article covers results of studies concerning adenylic system state in RBC and tissues (lungs; liver, kidneys, heart, brain) of rats exposed to acute and chronic inhalation of chemical pollutants widely used in petrochemical and oil-processing industries. Findings are that the animals subjected to ecologic toxic agents have significantly decreased ATP level, ADP and AMF accumulation in tissues and RBC.

Heterocyclic aromatic amine intake increases colorectal adenoma risk: findings from a prospective European cohort study.

BACKGROUND: Heterocyclic aromatic amines (HCAs), which arise from cooking meat and fish at high temperatures, may increase the risk of colorectal adenomas. Conversely, flavonoids might counteract the negative effects of HCAs. OBJECTIVE: The association between dietary HCA intake and colorectal adenoma incidence was investigated in a prospective cohort study. DESIGN: At recruitment (1994-1998), detailed information on diet, anthropometric measures, lifestyle, and medication use was assessed in 25,540 participants of the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort study. Dietary HCA intake was estimated by using information from food-frequency questionnaires on meat consumption, applied cooking methods, and preferred degree of browning. Until June 2007, 516 verified incident colorectal adenomas were identified. Participants with negative colonoscopy (n = 3966) were also included in the analytic cohort. Multivariate Cox proportional hazards regression was used to examine the association between colorectal adenoma risk and intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx). RESULTS: In multivariate analyses, the intake of PhIP as the most abundant dietary HCA was associated with an increased risk of colorectal adenoma (relative risk: 1.47; 95% CI: 1.13, 1.93; quartile 4 compared with quartile 1; P for trend = 0.002), but no statistically significant associations were observed for MeIQx and DiMeIQx intakes. In addition, adenoma risk also increased with the consumption of strongly or extremely browned meat (P for trend = 0.04). The association of PhIP intake with adenoma risk was most pronounced for small adenomas (P for trend = 0.01) and adenomas localized in the distal colon (P for trend = 0.002). CONCLUSION: The results of this first European cohort study support data from case-control studies of a positive association between HCA intake and colorectal adenoma risk.