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1.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 203-236, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31795923

RESUMEN

Since the inception of the IARC Monographs Programme in the early 1970s, this Programme has developed 119 Monograph Volumes on more than 1000 agents for which there exists some evidence of cancer risk to humans. Of these, 120 agents were found to meet the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs, compiled in 2008-2009 and published in 2012, provided a review and update of the 107 Group 1 agents identified as of 2009. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. The Group I agents reviewed in Volume 100, as well as five additional Group 1 agents defined in subsequent Volumes of the Monographs, were used to assess the degree of concordance between sites where tumors originate in humans and experimental animals including mice, rats, hamsters, dogs, and non-human primates using an anatomically based tumor nomenclature system, representing 39 tumor sites and 14 organ and tissue systems. This evaluation identified 91 Group 1 agents with sufficient evidence (82 agents) or limited evidence (9 agents) of carcinogenicity in animals. The most common tumors observed in both humans and animals were those of the respiratory system including larynx, lung, and lower respiratory tract. In humans, respiratory system tumors were noted for 31 of the 111 distinct Group 1 carcinogens identified up to and including Volume 109 of the IARC Monographs, comprising predominantly 14 chemical agents and related occupations in category VI; seven arsenic, metals, fibers, and dusts in category III, and five personal habits and indoor combustions in category V. Subsequent to respiratory system tumors, those in lymphoid and hematopoietic tissues (26 agents), the urothelium (18 agents), and the upper aerodigestive tract (16 agents) were most often seen in humans, while tumors in digestive organs (19 agents), skin (18 agents), and connective tissues (17 agents) were frequently seen in animals. Exposures to radiation, particularly X- and γ-radiation, and tobacco smoke were associated with tumors at multiple sites in humans. Although the IARC Monographs did not emphasize tumor site concordance between animals and humans, substantial concordance was detected for several organ and tissue systems, even under the stringent criteria for sufficient evidence of carcinogenicity used by IARC. Of the 60 agents for which at least one tumor site was identified in both humans and animals, 52 (87%) exhibited tumors in at least one of the same organ and tissue systems in humans and animals. It should be noted that some caution is needed in interpreting concordance at sites where sample size is particularly small. Although perfect (100%) concordance was noted for agents that induce tumors of the mesothelium, only two Group 1 agents that met the criteria for inclusion in the concordance analysis caused tumors at this site. Although the present analysis demonstrates good concordance between animals and humans for many, but not all, tumor sites, limitations of available data may result in underestimation of concordance.


Asunto(s)
Carcinogénesis/inducido químicamente , Carcinógenos/toxicidad , Neoplasias/inducido químicamente , Animales , Animales de Laboratorio , Humanos , Neoplasias/patología , Especificidad de la Especie
2.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 288-359, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31631808

RESUMEN

This review summarizes the carcinogenic mechanisms for 109 Group 1 human carcinogens identified as causes of human cancer through Volume 106 of the IARC Monographs. The International Agency for Research on Cancer (IARC) evaluates human, experimental and mechanistic evidence on agents suspected of inducing cancer in humans, using a well-established weight of evidence approach. The monographs provide detailed mechanistic information about all carcinogens. Carcinogens with closely similar mechanisms of action (e.g. agents emitting alpha particles) were combined into groups for the review. A narrative synopsis of the mechanistic profiles for the 86 carcinogens or carcinogen groups is presented, based primarily on information in the IARC monographs, supplemented with a non-systematic review. Most carcinogens included a genotoxic mechanism.


Asunto(s)
Carcinogénesis/inducido químicamente , Carcinógenos/toxicidad , Neoplasias/inducido químicamente , Animales , Humanos , Mutágenos/toxicidad , Neoplasias/patología
3.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 237-243, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31612803

RESUMEN

Volume 100 in the series of IARC Monographs on the Evaluation of Carcinogenic Risks to Humans comprises an update and review of relevant information on all agents determined to induce cancer in humans. These Group 1 agents are categorized in 6 Monographs (Volumes 100A-F) published in 2012. This paper describes the methodology and stringent criteria used in the creation of a comprehensive database on tumors noted in animals and humans for the carcinogens reviewed in Volume 100, and for additional Group 1 agents that were identified in subsequent Monographs through Volume 109. The development of this database involved the systematic collection of relevant data on tumors detected in humans and experimental animals identified by the Working Groups that conducted evaluations reported in the IARC Monographs. The database includes all human tumor sites identified by the Working Groups, along with all tumor sites for which there was sufficient evidence in experimental animals. This database provides a basis for assessing the degree of concordance between tumor sites observed in humans and experimental animals for Group 1 agents identified through Volume 109.


Asunto(s)
Carcinógenos/toxicidad , Bases de Datos Factuales , Neoplasias/inducido químicamente , Animales , Animales de Laboratorio , Humanos , Neoplasias/patología
4.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 244-263, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31637961

RESUMEN

Since the inception of the International Agency for Research on Cancer (IARC) in the early 1970s, the IARC Monographs Programme has evaluated more than 1000 agents with respect to carcinogenic hazard; of these, up to and including Volume 119 of the IARC Monographs, 120 agents met the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs provided a review and update of Group 1 carcinogens. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers, and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. Data on biological mechanisms of action (MOA) were extracted from the Monographs to assemble a database on the basis of ten key characteristics attributed to human carcinogens. After some grouping of similar agents, the characteristic profiles were examined for 86 Group 1 agents for which mechanistic information was available in the IARC Monographs up to and including Volume 106, based upon data derived from human in vivo, human in vitro, animal in vivo, and animal in vitro studies. The most prevalent key characteristic was "is genotoxic", followed by "alters cell proliferation, cell death, or nutrient supply" and "induces oxidative stress". Most agents exhibited several of the ten key characteristics, with an average of four characteristics per agent, a finding consistent with the notion that cancer development in humans involves multiple pathways. Information on the key characteristics was often available from multiple sources, with many agents demonstrating concordance between human and animal sources, particularly with respect to genotoxicity. Although a detailed comparison of the characteristics of different types of agents was not attempted here, the overall characteristic profiles for pharmaceutical agents and for chemical agents and related occupations appeared similar. Further in-depth analyses of this rich database of characteristics of human carcinogens are expected to provide additional insights into the MOA of human cancer development.


Asunto(s)
Carcinógenos/toxicidad , Mutágenos/toxicidad , Neoplasias/inducido químicamente , Animales , Carcinogénesis/inducido químicamente , Pruebas de Carcinogenicidad , Humanos , Agencias Internacionales , Mutagénesis , Neoplasias/patología
5.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 264-287, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31379270

RESUMEN

A database on mechanistic characteristics of human carcinogenic agents was developed by collecting mechanistic information on agents identified as human carcinogens (Group 1) by the International Agency for Research on Cancer (IARC) in the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. A two-phase process is described for the construction of the database according to 24 toxicological endpoints, derived from appropriate test systems that were acquired from data obtained from the mechanisms sections of the IARC Monographs (Section 4) and a supplementary PubMed search. These endpoints were then aligned with 10 key characteristics of human carcinogens that reflect the broader attributes of these agents relating to the development of cancer in humans. The considerations involved in linking of toxicological endpoints to key characteristics are described and specific examples of the determination of key characteristics for six specific agents (tamoxifen, hepatitis B virus, arsenic, ultraviolet and solar radiation, tobacco smoking, and dioxin) are provided. Data for humans and animals were tabulated separately, as were results for in-vivo and for in-vitro sources of information. The database was constructed to support a separate analysis of the expression of these endpoints by 86 Group 1 carcinogens, in-vivo and in-vitro along with an analysis of the key characteristics of these agents.


Asunto(s)
Carcinógenos/toxicidad , Bases de Datos Factuales , Neoplasias/inducido químicamente , Animales , Carcinogénesis/inducido químicamente , Pruebas de Carcinogenicidad , Humanos
6.
Pneumonol Alergol Pol ; 83(3): 193-202, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26050979

RESUMEN

INTRODUCTION: COPD is one of the most frequent respiratory diseases responsible for patients' disability and mortality. In 2005 a single primary care practice, COPD was diagnosed in 183 out of 1,960 eligible subjects ≥ 40 years (9.3%). The aim of this study was to assess mortality rate and causes of deaths in this group after 6 years. MATERIAL AND METHODS: In 2011 we invited all 183 patients with COPD recognised in 2005. We performed spirometry, physical examination, questionnaire of respiratory symptoms, smoking habits, concomitant diseases and treatment. Information about deaths was taken from primary care register, furthermore, family members were asked to deliver medical documentation or death certificate. RESULTS: In 2011 we studied only 74 subjects (40.4%), 43 subjects died (23.5%) and 66 subjects were lost from the follow-up (36.1%). Cardiovascular diseases were the most frequent causes of deaths - 21 subjects (48.8%) (heart attack - 8 patients and stroke - 8 patients). Respiratory failure in the course of COPD exacerbation was the cause of 10 deaths (23.3%). Neoplastic diseases lead to 9 deaths (20.9%) (lung cancer 7 patients). Renal insufficiency was responsible for one death (2.325%), and the causes of 2 deaths remained unknown (4.65%). Subjects who died (predominantly males) were older, had higher MRC score and lower FEV1. CONCLUSIONS: Study performed six years after COPD diagnosis revealed that 23.5% of subjects died. The main causes of deaths were the following: cardiovascular diseases (mainly heart attack and stroke), COPD exacerbations and lung cancer (more than 75%). Death risk in COPD patients was associated with age, male sex, dyspnoea and severity of the disease.


Asunto(s)
Causas de Muerte , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Disnea , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Fumar/mortalidad , Espirometría , Accidente Cerebrovascular/mortalidad , Encuestas y Cuestionarios , Factores de Tiempo
7.
Eur Respir J ; 45(5): 1228-38, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25766977

RESUMEN

Few data exist on respiratory effects of indoor air quality and comfort parameters in the elderly. In the context of the GERIE study, we investigated for the first time the relationships of these factors to respiratory morbidity among elderly people permanently living in nursing homes in seven European countries. 600 elderly people from 50 nursing homes underwent a medical examination and completed a standardised questionnaire. Air quality and comfort parameters were objectively assessed in situ in the nursing home. Mean concentrations of air pollutants did not exceed the existing standards. Forced expiratory volume in 1 s/forced vital capacity ratio was highly significantly related to elevated levels of particles with a 50% cut-off aerodynamic diameter of <0.1 µm (PM0.1) (adjusted OR 8.16, 95% CI 2.24-29.3) and nitrogen dioxide (aOR 3.74, 95% CI 1.06-13.1). Excess risks for usual breathlessness and cough were found with elevated PM10 (aOR 1.53 (95% CI 1.15-2.07) and aOR 1.73 (95% CI 1.17-10.3), respectively) and nitrogen dioxide (aOR 1.58 (95% CI 1.15-2.20) and aOR 1.56 (95% CI 1.03-2.41), respectively). Excess risks for wheeze in the past year were found with PM0.1 (aOR 2.82, 95% CI 1.15-7.02) and for chronic obstructive pulmonary disease and exhaled carbon monoxide with formaldehyde (aOR 3.49 (95% CI 1.17-10.3) and aOR 1.25 (95% CI 1.02-1.55), respectively). Breathlessness and cough were associated with higher carbon dioxide. Relative humidity was inversely related to wheeze in the past year and usual cough. Elderly subjects aged ≥80 years were at higher risk. Pollutant effects were more pronounced in the case of poor ventilation. Even at low levels, indoor air quality affected respiratory health in elderly people permanently living in nursing homes, with frailty increasing with age. The effects were modulated by ventilation.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Casas de Salud , Ventilación , Anciano , Anciano de 80 o más Años , Monóxido de Carbono/análisis , Exposición a Riesgos Ambientales , Monitoreo del Ambiente/métodos , Europa (Continente) , Femenino , Formaldehído/análisis , Anciano Frágil , Estado de Salud , Viviendas para Ancianos , Humanos , Masculino , Dióxido de Nitrógeno/química , Ozono/análisis , Material Particulado/análisis , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Ruidos Respiratorios , Factores de Riesgo , Encuestas y Cuestionarios
8.
Multidiscip Respir Med ; 8(1): 71, 2013 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-24262306

RESUMEN

BACKGROUND: Indoor air pollution (IAP) constitutes a major global public health problem requiring increasing efforts in research and policymaking that may have special significance for elderly that are likely to spend most of their day indoors and appear to be particularly susceptible to adverse effects of chemical pollutants and bio-contaminants. Yet, evidence existing on the effects of IAP in elderly is scanty. The Geriatric study in Europe on health effects of air quality in nursing homes (GERIE) study aimed to assess health effects of major indoor air pollutants and thermal conditions in elderly (> 70 years) living stably in nursing homes (NH) across Europe. Respiratory effects were particularly considered as airways and lung constitute the first target of air pollutants. OBJECTIVES: We describe here the rationale and the methods of the GERIE Study. METHODS: 8 nursing homes were randomly selected in 7 European countries. Twenty individuals were randomly selected in each nursing home. Major indoor and outdoor air chemical pollutants (PM10, PM2.5, PM0.1, formaldehyde, NO2; O3, VOC, CO2) and bio-contaminants (moulds, allergens) were assessed objectively with standardized procedures. Major health status indicators were assessed through a standardized questionnaire, non-invasive clinical tests and blood and urine biomarkers as well as saliva for ADN. RESULTS: The GERIE study has given the opportunity to publish two reviews on respiratory health effects of indoor and outdoor air pollution in elderly. In addition it has provided the inventory of air quality and thermal conditions in 50 nursing homes across Europe and data on respiratory health status in 600 elderly aged 82 years in mean. Major future results will include the relationships between NH environment and health in elderly. CONCLUSIONS: The main long-term purpose of the GERIE study is to improve the health of elderly who permanently reside in nursing homes or of those who are exposed to indoor air pollution because of reduced mobility.

9.
Pneumonol Alergol Pol ; 81(5): 417-23, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23996880

RESUMEN

INTRODUCTION: Metabolic syndrome (MS), which is connected with enlarged cardiovascular risk, is common in patients with OSAS. The aim of the study was to estimate the prevalence of MS in patients with OSAS according to two definitions of MS (criteria from NCEP-ATP III from 2001 versus criteria from IDF 2005). MATERIAL AND METHODS: Materials consisted of 155 males and 18 females with OSAS (mean AHI 44 ± 22 h-1), obesity (BMI 31.8 ± 5.0 kg/m2), aged 53.9 ± 9.3 years (mean ± SD). Serum lipids, glucose, body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were measured in all patients. RESULTS: According to first definition (NCEP - ATP III from 2001), MS was diagnosed in 98 patients (56% of the whole group - MS1 group) compared to 120 patients (69% of the whole group - MS2 group) diagnosed according to the second definition (IDF from 2005), p < 0.05. No differences in BMI and WC between the groups were found. Significant differences in WHR were noted (MS1 group: 1.005 ± 0.05 vs. MS2 group: 1.027 ± 0.06, p < 0.05). Patients from the MS2 group had higher cholesterol HDL compared to the MS1 group (52.3 ± 12.1 mg/dl vs. 42.3 ± 12.1 mg/dl, p < 0.05). Serum triglyceride concentrations were significantly higher in the MS1 group than in the MS2 group (228 ± 122 mg/dl vs. 122 ± 49 mg/dl, p < 0.05). There were no differences in OSAS severity between the MS1 and MS2 group. In both groups weak correlations between diagnosis of MS and AHI were found (r = 0.19 for MS1 and r = 0.21 for MS2, p < 0.05) They are, however, clinically insignificant. CONCLUSIONS: The IDF definition from 2005 of metabolic syndrome indeed increases the frequency of diagnosis of metabolic syndrome in patients with OSAS. We did not observe essential clinical correlation among the degree of OSAS severity and recognition of metabolic syndrome in the MS1 or in the MS2 group.


Asunto(s)
Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Adulto , Distribución por Edad , Anciano , Índice de Masa Corporal , Comorbilidad , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Circunferencia de la Cintura
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