IARC scientific publications最新文献

Control strategies to minimize mycotoxin levels in food comprise several broad categories, including good agricultural practice, good manufacturing practice, and hazard analysis and critical control point principles. In general, intervention strategies include pre-harvest, post-harvest, and dietary approaches, depending on the specific mycotoxins and the food commodity likely to be contaminated. This chapter describes practical interventions, which are arranged by the major groups of mycotoxins and are described according to their stage of development, efficacy, geographical regions in which they have been tested or applied, simplicity or complexity, and breadth of usefulness. Typical pre-harvest interventions include the breeding of resistant plant cultivars, good agricultural practice, and biocontrol using non-toxigenic strains. Post-harvest interventions include the removal of infected and/or insect-damaged food components by sorting, maintaining correct drying and storage conditions, and chemical deactivation such as nixtamalization. Dietary interventions include reducing mycotoxin bioavailability or modulating metabolism in ways that reduce the harmful effects of reactive metabolites. Cost-effective and simple intervention methods, predominantly at the population level, should be emphasized in developing countries, where resources are limited and sophisticated technologies are lacking.

Risk assessment is the process of quantifying the magnitude and exposure, or probability, of a harmful effect to individuals or populations from certain agents or activities. Here, we summarize the four steps of risk assessment: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Risk assessments using these principles have been conducted on the major mycotoxins (aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, and zearalenone) by various regulatory agencies for the purpose of setting food safety guidelines. We critically evaluate the impact of these risk assessment parameters on the estimated global burden of the associated diseases as well as the impact of regulatory measures on food supply and international trade. Apart from the well-established risk posed by aflatoxins, many uncertainties still exist about risk assessments for the other major mycotoxins, often reflecting a lack of epidemiological data. Differences exist in the risk management strategies and in the ways different governments impose regulations and technologies to reduce levels of mycotoxins in the food-chain. Regulatory measures have very little impact on remote rural and subsistence farming communities in developing countries, in contrast to developed countries, where regulations are strictly enforced to reduce and/or remove mycotoxin contamination. However, in the absence of the relevant technologies or the necessary infrastructure, we highlight simple intervention practices to reduce mycotoxin contamination in the field and/or prevent mycotoxin formation during storage.

Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors influencing their growth and the various susceptible commodities that are contaminated. Finally, decision trees are included to assist the user in making informed choices about the likely mycotoxins present in the various crops.

Unexplained disease outbreaks in farm and domestic animals have suggested the likely presence of mycotoxins in feeds for many years. The manifestations of mycotoxicoses in the field are frequently nondescript and potentially have many contributing factors, which are often difficult to define. Nevertheless, toxigenic moulds were implicated in, and sometimes proven to be the cause of, animal disease in field outbreaks long before the toxins were discovered. The development of methods for the chemical analysis of mycotoxins in feeds and animal tissues has contributed to an improved understanding of the dose-response relationships of farm animal diseases associated with exposure to aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. In all cases the effect of mycotoxins on animal performance is potentially a major problem for farmers regardless of their scale of operation. Reduced growth, decreased egg and milk production, lower reproductive efficiency, and increased susceptibility to stress are all potentially devastating consequences of mycotoxin exposure. Thus, being aware of the outward signs that might signal the involvement of a mycotoxin in an animal performance problem is the first step to minimizing potential adverse impacts. The target organ affected can provide important clues to involvement of a specific mycotoxin, in which case understanding the toxicokinetics and toxicology will assist in minimizing the cost and maximizing the effectiveness of interventions. The primary objective of this chapter is to provide information that will aid in the field identification of the possible involvement of a mycotoxin in an animal production problem. In conjunction with the information provided in the other chapters, this information will assist farmers in making decisions that will minimize losses due to diseases induced by mycotoxins.

Mycotoxins have been investigated in relation to a wide range of adverse human health effects, but the evidence for all but a small number of associations is limited. Thus, the full impact on human health of the widespread exposure to mycotoxins remains to be defined. The main exception is for aflatoxins; epidemiological, experimental, and mechanistic studies have contributed to establishing aflatoxins as a cause of human liver cancer, with a particularly elevated risk in people chronically infected with hepatitis B virus. In addition, acute aflatoxicosis after exposure to high dietary toxin levels has been demonstrated. The impairment of child growth by aflatoxin exposure early in life remains an important subject of study. More information is also required on the potential immune effects of aflatoxins, especially in vulnerable populations. For fumonisins, studies indicate a possible role in oesophageal cancer and in neural tube defects, although no definitive conclusions can be drawn at present. For deoxynivalenol and other trichothecenes, exposure has been linked to acute poisoning outbreaks in large numbers of subjects. For ochratoxin A and zearalenone, the human health effects remain undefined. The limited tools available to accurately assess human exposure to mycotoxins and the relative paucity of epidemiological studies need to be addressed if the full extent of the adverse effects of these common dietary contaminants is to be understood and adequate public health measures taken. In this respect, newly established biomarkers of exposure at the individual level are proving valuable in improving exposure assessment in epidemiological studies.

The Qidong cancer registry was established in 1972, and registration of cases is done by active and passive methods. The registry contributed data on 33 cancer sites or types registered during 1992-2000 for this survival study. Data on 22 cancers registered during 1972-2000 were utilized to elicit the survival trend by period and cohort approaches. Follow-up was done by a mixture of active and passive methods, with median follow-up ranging from 2-25 months. The proportion of cases with histologically verified cancer diagnosis ranged from 9-100%, and 87-100% of total registered cases were included for survival analysis. The top-ranking cancers on 5-year age-standardized relative survival (%) were thyroid (78%), breast (58%), corpus uteri (54%), larynx (51%) and urinary bladder (42%). The corresponding survival rates for common cancers were liver (6%), lung (7%) and stomach (18%). The 5-year relative survival by age group fluctuated and showed no distinct pattern or trend. The comparison of 5-year relative survival trend by cohort and period approaches revealed that period survival closely predicted the survival experience of cancer cases diagnosed in that period for most cancers.

The Costa Rica national tumour registry was founded in 1976 and nationwide data collection commenced in 1980. Cancer registration is predominantly done by passive methods. The registry contributed data on survival for invasive cancers of breast and cervix and in situ cancer of the cervix registered during 1995-2000. Followup has been carried out predominantly by passive methods, with median follow-up ranging from 31-47 months. The proportion of cases with histological confirmation of cancer diagnosis was 92% for invasive cancers and almost 100% for in-situ cancer of the cervix; death certificates only (DCOs) comprised 3%, and 78-86% of total cases registered were included for survival analysis. The one-, three- and five-year relative survival were 93%, 77% and 68%, respectively for breast cancer; the corresponding figures for invasive cervix cancer were 83%, 61% and 54%, respectively. The five-year relative survival for in-situ cervix cancer was 99%. A decreasing survival with increasing age group at diagnosis was noted for in-situ cancer of the cervix, while it fluctuated for invasive breast and cervix cancers. A decreasing survival with increasing clinical extent of disease was noted for invasive breast and cervix cancers.

The population-based cancer registry in Cuba is a national cancer registry established in 1964; cancer registration is entirely done by passive methods. Data on survival from 13 cancer sites or types registered during 1994-1995 are reported. Follow-up has been carried out predominantly by passive methods, with median follow-up ranging from 13-54 months. The proportion with histologically verified diagnosis for various cancers ranged between 34-100%; death certificates only (DCOs) comprised 8-50%; 50-89% of total registered cases were included for the survival analysis. The 5-year age-standardized relative survival for selected cancers were breast (69%), colon (41%), cervix (56%), urinary bladder (64%), rectum (48%) and non-Hodgkin lymphoma (49%). The 5-year relative survival by age group showed no distinct pattern or trend, and was fluctuating. A decreasing survival with increasing clinical extent of disease was noted for all cancers studied. The data on survival trend revealed that the 5-year relative survival of most cancers diagnosed in 1994-1995 was greater than that in 1988-1989.

The national cancer registry of the Gambia was established in 1986 as part of the Gambia Hepatitis Intervention Study in collaboration with IARC, France; Medical Research Council (MRC) Laboratories of the UK; and the Government of the Gambia at MRC, Banjul. Registration of incident cancer cases is done by active and passive methods. For this study, the registry contributed data on survival for six cancer sites or types registered during 1993-1997. Follow-up has been carried out predominantly by active methods with median follow-up ranging between 1-6 months. The proportion of histologically verified diagnosis for various cancers ranged between 1-45%, and 54-82% of total registered cases were included for survival analysis. Complete follow-up at five years from the incidence date ranged between 81-98% for different cancers. The 5-year age-standardized relative survival for selected cancers were cervix (23%), non-Hodgkin lymphoma (22%), breast (10%), stomach (4%) and liver (3%). The 5-year relative survival by age group showed fluctuations with no definite pattern or trend emerging, and with no survivors in many age intervals.

Biological monitoring is the analysis of human biological materials for a substance of interest and/or its metabolites (biomarkers) or a biochemical change that occurs as a result of an exposure to provide a quantitative measure of exposure or dose. These measures can be used in epidemiological studies either directly as estimates of exposure or indirectly in the calibration of other exposure assessment methods, such as questionnaires. This chapter will discuss important methodological considerations for the implementation of biomarkers of exogenous exposure in epidemiology by focusing on biomarker characteristics (e.g. variability, half-life) and their application in different study designs.