Exposure and risk characterizations of ochratoxins A and aflatoxins through maize (Zea mays) consumed in different agro-ecological zones of Ghana.

Mycotoxin contamination of foodstuffs is a serious food safety concern globally as the prolonged ingestion of these toxins has the tendency to worsen the risk of hepatocellular carcinoma. This study aimed at estimating ochratoxin A (OTA) and aflatoxin (AF) levels above international (European Food Safety Authority, EFSA) and local (Ghana Standards Authority, GSA) standards as well as the health risks associated with the consumption of maize (n = 180) sampled from six (6) regions representing the agro-ecological zones of Ghana. OTA and AF were measured with High-Performance Liquid Chromatography with a Fluorescence detector. Out of the 180 samples analyzed for total aflatoxins (AFtotal), 131/180 tested positive and 127 (70.50%) exceeded the limits of EFSA and ranged 4.27-441.02 µg/kg. While for GSA, 116 (64.44%) of samples exceeded this limit and ranged between 10.18 and 441.02 µg/kg. For OTA, 103/180 tested positive and 94 (52.22%) of samples between the range 4.00-97.51 µg/kg exceeded the tolerable limit of EFSA, whereas 89 (49.44%) and were in the range of 3.30-97.51 µg/kg exceeded the limits of GSA. Risk assessment values for total aflatoxins (AFtotal) ranged between 50 and 1150 ng/kg bw/day, 0.4-6.67, 0-0.0323 aflatoxins ng/kg bw/day and 1.62-37.15 cases/100,000 person/year for Estimated Daily Intake (EDI), Margin of Exposure (MOE), Average Potency, and Cancer Risks respectively. Likewise, ochratoxin (OTA) values were in the ranges of 8.6 × 10-3-450 ng/kg bw/day, 0.05-2059.97, 0-0.0323 ochratoxins ng/kg bw/day and 2.78 × 10-4-14.54 cases/100,000 person/year. Consumption of maize posed adverse health effects in all age categories of the locations studied since the calculated MOE values were less than 10,000.

Investigation of a Novel Multicomponent Mycotoxin Detoxifying Agent in Amelioration of Mycotoxicosis Induced by Aflatoxin-B1 and Ochratoxin A in Broiler Chicks.

The present study was designed to determine the efficacy of a novel multicomponent mycotoxin detoxifying agent (MMDA) containing modified zeolite (Clinoptilolite), Bacillus subtilis, B. licheniformis, Saccharomyces cerevisiae cell walls and silymarin against the deleterious effects of Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) in broiler chicks. A total of 160 one-day-old Ross 308® broiler chicks were randomly allocated in four treatment groups, with four replicates, according to the following experimental design for 42 days. Group A received a basal diet; Group B received a basal diet contaminated with AFB1 and OTA at 0.1 mg/kg and 1 mg/kg, respectively; Group C received a basal diet contaminated with AFB1 and OTA and MMDA at 1 g/kg feed, and Group D received a basal diet contaminated with AFB1 and OTA and MMDA at 3 g/kg feed. Results showed that ingested mycotoxins led to significant (p ≤ 0.05) reduction in body weight and feed conversion from 25 days of age, induced histopathological changes, increased the pH of the intestinal content, and altered the biochemical profile of birds with significantly (p ≤ 0.05) increased aspartate aminotransferase (AST) values (p ≤ 0.05). On the other hand, the supplementation of MMDA significantly (p ≤ 0.05) improved the feed conversion ratio (FCR) during the second part of the study, diminished biochemical alterations, reduced pH in jejunal and ileal content, and E. coli counts in the caeca of birds (p ≤ 0.05). It may be concluded that the dietary supplementation of the MMDA partially ameliorated the adverse effects of AFB1 and OTA in broilers and could be an efficient tool in a mycotoxin control program.

Ochratoxin A and aristolochic acid involvement in nephropathies and associated urothelial tract tumours.

This review addresses the unresolved aetiology of several nephropathies and associated upper tract tumours diagnosed all over the world, but especially in the Balkan regions. Studies conducted over the last 35 years point to mycotoxins, mainly ochratoxin A (OTA) as the main culprit. Recent theories however have implicated aristolochic acids (AA). The aim of this review is to put forward arguments in favour of the mycotoxin theory and to show the incoherence of the AA theory. It discusses the differences between the epidemiology of Balkan endemic nephropathy (BEN) and aristolochic acid nephropathy (AAN); OTA and AA carcinogenicity; clinical and pathological effects induced by OTA and AA; sources of OTA contamination (food, air, drinking water); OTA- and AA-DNA adduct formation; the role of genetic polymorphisms; and the risk for young children.

Mycotoxic and aristolochic acid theories of the development of endemic nephropathy.

Despite many efforts of scientists and epidemiologists, the aetiology of endemic nephropathy (EN) is still unknown. This disease occurs in the rural population of geographically limited areas of Bulgaria, Bosnia and Herzegovina, Croatia, Romania, and Serbia, and a number of theories have been proposed about its aetiology. The mycotoxin theory has prevailed until now, based on the studies of nephrotoxic mycotoxin ochratoxin A (OTA) that revealed higher frequency of OTA-positive food and blood samples in endemic than in non-endemic areas.However, a new aristolochic acid (AA) theory of EN origin has been proposed recently, due to the histological similarities in kidney lesions between patients suffering from EN and patients suffering from Chinese herbs nephropathy caused by AA. Until now it has not been unequivocally proved that the inhabitants of EN areas are exposed to higher concentration of AA than in other regions and the exposure pathways are rather uncertain. This paper presents most important studies supporting both theories, indicating also the inconsistencies of each.

Ocratoxina A em suínos: revisão de literatura / Ochratoxins A in swine: review literature

As intoxicações causadas pela ingestão de alimentos contaminados por certos fungos são responsáveis por diversos problemas de saúde, tanto em animais como no homem.Os agentes produzem substâncias conhecidas pelo nome genérico de micotoxinas. Estas compreendem um conjunto complexo de substâncias químicas, diferenciando-se das toxinas bacterianas, por não serem de natureza protéica e não serem imunogênicas. São substâncias termoestáveis e fotorresistentes, que apresentam um longo período de atividade tóxica nos gêneros alimentícios, mesmo após o desaparecimento dos fungos que lhes deram origem. Entre as toxinas de maior importância em alimentos, estão as ocratoxinas. Pelo menos nove tipos diferentes de ocratoxinas já foram identificados, sendo que a ocratoxina A é a mais encontrada. Ela tem sido alvo de muitas pesquisas, por ter uma potente ação nefrotóxica. Devido às suas propriedades físico-químicas, a ocratoxina é facilmente absorvida no trato gastrointestinal, tendo uma biodisponibilidade superior a 50 por cento em muitas espécies de mamíferos. Apresenta uma alta afinidade pelas proteínas plasmáticas, o que determina sua persistência no organismo, sendo eliminada pelas vias renal e hepatobiliar, além da secreção láctea. Várias alterações patológicas em suínos alimentados com rações elaboradas a partir de grãos contaminados com ocratoxina A podem ser observadas e, dependendo do nível de contaminação, podem levar à morte destes animais em poucos dias...

[Ochratoxin A and human health].

Ochratoxin A (OA) is produced mainly by Penicillium verrucosum, Aspergillus ochraceus and A. carbonarius and it was found as a contaminant in the large number of agricultural commodities, feedstuffs and animal organs such as kidney and liver of pig. Toxicological studies indicated that OA is a teratogenic, mutagenic and carcinogenic mycotoxin with the strong toxic effects on liver and kidney. In some endemic areas in the world, OA was suspected to be related to swine nephropathy and has been detected in blood samples from inhabitants in these areas as well. More and more attention was paid to the relationship between the consumption of food contaminated with OA and human health. In this paper, OA--producing fungi, the contamination of it to the agricultural commodities, its toxicity and risk assessment are reviewed.

Toxigenic fungi and mycotoxins.

Growth of commonly occurring filamentous fungi in foods may result in production of toxins known as mycotoxins, which can cause a variety of ill effects in humans, from allergic responses to immunosuppression and cancer. The most important mycotoxins are aflatoxins, ochratoxin A, fumonisins, trichothecenes and zearalenone. Aflatoxins are potent carcinogens and, in association with hepatitis B virus, are responsible for many thousands of human deaths per annum, mostly in non-industrialised tropical countries. Ochratoxin A is a probable carcinogen, and may cause urinary tract cancer and kidney damage in people from northern and eastern Europe. Fumonisins appear to be the cause of oesophageal cancer in southern Africa, parts of China and elsewhere. Trichothecenes are highly immunosuppressive and zearalenone causes oestrogenic effects in animals and man. Currently available records and statistics do not reflect the major role played by mycotoxins in mortality attributable to food-borne micro-organisms.

Alterations in total and differential counts of WBC during ochratoxicosis in rabbits.

Consumption of ochratoxin-contaminated feed (10 mg/kg) by young rabbits for 90 days altered total and differential counts of WBC. Time dependent decline in WBC count indicates occurrence of cumulative toxicity.

Severe hepatopathy in geese and broilers associated with ochratoxin in their feed.

The feeding of a shipment of imported corn was associated with a severe reduction in growth and increased mortality in geese, and increased mortality in broilers. Pathological examinations revealed hepatopathy, visceral gout and mild nephropathy in geese, and in broilers an hepatopathy, which was often severe, and ascites. Samples of feed from affected geese farms were examined for up to 24 mycotoxins, and ochratoxin was found in 6 of 15 samples at levels up to 930 ng/g. The syndrome was experimentally reproduced by feeding geese and broilers suspect feeds with the natural ochratoxin contamination. It is believed that another, unidentified, mycotoxin was the major cause of the hepatotoxicity, and that ochratoxin served in this case as an indicator of a multi-mycotoxin involvement.

[Experimental and human nephrotoxicity induced by ochratoxins]. / Néphrotoxicité expérimentale et humaine des ochratoxines.

Ochratoxin A is a mycotoxin: a dihydroisocoumarin derivative linked to L. beta phenylalanine. Ochratoxin A is produced by a number of Aspergillus and Penicillium species. This mycotoxin is a carcinogenic, teratogenic, mutagenic and immunosuppressive substance. Ochratoxin A is a common contaminant found in a variety of foods for human nutrition as well as animal feeds. The aim of this study is to discuss nephrotoxic properties of this mycotoxin in humans. Nephrotoxicity has been reported in many animals after exposure to ochratoxin A. Porcine nephropathy due to this mycotoxin is a well known disease characterized by impairment of proximal renal function. Renal damage is also confined to the proximal tubule in other animal species. A good correlation is found between renal function abnormalities and the location of the lesions along the nephron. Of particular interest is the presence of nuclear abnormalities of the epithelial cells with pyknosis, karyorrhexis and karyomegaly. The question is to know if ochratoxin is nephrotoxic in humans. Acute nephrotoxicity seems to be very rare and we found only one case report suggesting such a possibility. We observed the occurrence of chronic renal failure in two patients with a possible responsibility of a chronic ochratoxin A intoxication. Clinical and histologic findings in these two patients were quite similar to those described in several cases of karyomegalic interstitial nephritis. Striking similarities between the changes in renal structure and function seen in ochratoxin A-induced experimental nephropathies and in Balkan endemic nephropathy suggest a common etiologic agent. This mycotoxin could be also responsible for interstitial nephropathies in North Africa.

[Ochratoxin A, ubiquitous mycotoxin contaminating human food]. / L'ochratoxine A, mycotoxine ubiquitaire contaminant l'alimentation humaine.

Ochratoxin A (OTA) a mycotoxin produced by molds of the Aspergillus and Penicillium genera, contaminates animal feeds and human foods. It has been shown to induce renal adenomas and hepatocellular carcinomas in rodents. OTA is implicated in Balkan endemic nephropathy, a disease followed by a high incidence of urinary tract tumours. Concerning the genotoxicity of OTA, we have recently shown, using the [32P]-phosphate postlabelling method, that several DNA-adducts are formed in four mice organs treated with OTA. Some of the adducts were specific of every analyzed tissue. These results, allow us to state that OTA metabolism in different from organ to organ. The influence of OTA metabolism on its genotoxic effect was studied. Preliminary results have shown the possibilities of oxidative pathways in OTA metabolism leading to genotoxic compounds. Effects of some vitamins such as retinol (A), ascorbic acid (C) and tocopherol (E), which are known to act as superoxide anion scavengers, were tested on genotoxicity of OTA. Pretreatment of mice by vit E induced a decrease of the DNA-adducts by 80% in kidney, and by 55% in liver. Vit A and vit C decreased DNA-adduct levels by 70% in kidney. In liver, DNA adduct level was essentially decreased by vit C (90%). Vit A decreased only the level by 25% in this organ. The involvement of oxidative metabolism in the genotoxicity of OTA led us to investigate the effect of prostaglandin H synthase (PHS) which is known to cooxidase xenobiotics. Aspirin and indomethacin which inhibit this enzyme were given prior to OTA administration to mice in order to test this metabolic pathway. The decrease observed with aspirin was of about 90% and 30% in kidney and liver respectively, and of 90% and 80% with indomethacin in kidney and liver. These results confirmed that OTA is activated to genotoxic metabolites by cooxydation by the prostaglandin synthase route. Human bronchial epithelial cells (BEAS-2B) expressing or not human cytochrome P450s (CYP) (1A2, 2A6, 2D6, 2E1 and 3A4) were incubated with 0.5 microM OTA for 24 h. DNA-adducts were detected in all cells. Total DNA-adduct levels ranged from 4 to 85 adducts per 10(9) nucleotides. Some adducts were common to all cell types including cells expressing only normal phase II enzymes, but no cytochromes P450. Some other DNA-adducts were only induced by specific CYPs. The highest DNA-adduct level was found in cells where CYP 1A2 was expressed. Nevertheless, more different types of DNA-adducts were formed in cells expressing CYP 2D6.(ABSTRACT TRUNCATED AT 400 WORDS)

Health risk assessment of the mycotoxin ochratoxin A to humans: Czech Republic--Brno--1991/92.

In the course of year 1991 and 1992 about 594 blood donors of the Brno agglomeration in the Czech Republic were examined for the ochratoxin A content (OA) in blood serum. When higher concentrations of OA were found the blood donors were examined repeatedly (differentiation of acute or chronic exposure). A mean concentration of 0.63 microgram OA/l blood serum (0.30 microgram = geom.mean) was recorded. The assessed continuous mean daily dietary intake of OA was about 0.74 ng (0.35 ng = geom. mean) OA/kg b.w./day. The assessed continuous mean contamination of food groups (cereal and meat products) was about 0.65 microgram (0.31 microgram = geom. mean) OA/kg. In persons with elevated OA concentrations in blood serum the decrease was at the latest confirmed within 2 months after the test result. An accidental acute exposure was probably involved. Tolerable daily intake of OA (TDI) was determined with regard to the nephrotoxic, teratogenic, immunosuppressive and carcinogenic effect at the level of: 16,500, 250 and 5 ng OA/kg b.w./day. As a legislative limit TDI = 5 ng OA/kg b.w./day was suggested. The group of persons studied was probably not threatened by any of the health risks given.

A review of recent advances in understanding ochratoxicosis.

Ochratoxin A (OA) is a toxin that contains an isocoumarin moiety linked by a peptide bond to phenylalanine. It is produced by certain Penicillium (mainly P. verrucosum) and Aspergillus (mainly A. alutaceus) species of storage fungi. Total amounts of OA and other related toxins produced by these fungi are influenced by many factors. Several forms of OA have been discovered, some of which are highly toxic, whereas others have lower toxicity. Ochratoxin A has been detected in foods, feeds, animal tissues, and human blood in both Europe and North America. It has been implicated in the fatal human disease Balkan endemic nephropathy, has been shown to be a powerful carcinogen in rodents, and produces many other adverse effects in animals. It is absorbed passively throughout the gastrointestinal tract and in an active manner in the kidney. It is subjected to intestinal secretion and reabsorption via enterohepatic recycling. Binding of OA in the blood to the albumin fraction and recycling in the bile and kidney contributes to its long half-life in animals. Ochratoxin A is hydrolyzed to its nontoxic alpha form (O alpha) by microorganisms in the rumen, cecum, and large intestine. The toxin is excreted primarily in the urine as O alpha and to a lesser degree as OA; smaller amounts of OA and O alpha are generally excreted in the feces. Three distinct mechanisms of OA toxicity have been proposed; other toxic effects of OA seem to be secondary in nature. Several different strategies can be employed for controlling or neutralizing the effect of OA, including the use of proper storage conditions, the use of specific adsorbents to reduce absorption of OA, and the feeding OA-contaminated feedstuffs to ruminants. Antioxidants such as ascorbic acid have been shown to reduce the toxic effects of OA in laying hens. In summary, OA contamination of cereal food and feed may occur, given appropriate conditions. Implementation of suitable procedures may eliminate or minimize this potentially serious problem.

Mycotoxins and reproduction in domestic livestock.

Molds are parasitic plants that are ubiquitous in livestock feedstuffs. Even though molds themselves reduce the quality of grains, their synthesis of chemical substances termed mycotoxins causes the greatest monetary loss to the animal industry. Five major mycotoxins that impair growth and reproductive efficiency in North America are aflatoxins, zearalenone, deoxynivalenol, ochratoxin, and ergot. Aflatoxins are produced by Aspergillus flavus and Aspergillus parasiticus. Consumption of grains containing aflatoxins by swine affects reproduction indirectly by reducing feed intake and growth. In swine, aflatoxins impair liver and kidney function, delay blood clotting, increase susceptibility to bruising, and interfere with cellular humoral immune systems. Ruminants are comparatively resistant to aflatoxicosis, but presence of aflatoxins in milk of dairy cows is closely monitored for human safety. Depending on environmental conditions, Fusarium roseum can produce either zearalenone or deoxynivalenol. Days 7 to 10 postmating seem to be a critical period of gestation for zearalenone to exert its detrimental actions on early embryonic development. Presence of deoxynivalenol in swine feedstuffs decreases feed intake, causes feed refusal, and induces occasional vomiting. Several species of Penicillium and Aspergillus produce ochratoxin, a mycotoxin that causes necrosis of kidney tissue. Ergot alkaloids produced by Claviceps purpurea on wheat can cause reproductive problems and are associated with lactational failure in swine. Various methods have been developed to remove mycotoxins from infected feedstuffs. Chemical analyses in laboratories as well as diagnostic kits suitable for use at the elevator or farm can be used successfully to identify which mycotoxins are present in suspect feedstuffs.

Efficacy of hydrated sodium calcium aluminosilicate to reduce the individual and combined toxicity of aflatoxin and ochratoxin A.

A 2 x 2 x 2 factorial arrangement of treatments consisting of dietary aflatoxin (3.5 micrograms/g), ochratoxin A (2.0 micrograms/g), and hydrated sodium calcium aluminosilicate (HSCAS, .5%) was used to evaluate the individual and combined effects of these treatments. There were six replicate pens of 10 broilers per pen for each of the eight treatments. The broilers were maintained on these treatments from 1 day to 3 wk of age with feed and water available for ad libitum intake. Aflatoxin and ochratoxin A each significantly decreased body weight, serum protein, albumin, and cholesterol and increased the relative weight of the liver, kidney, and proventriculus. Aflatoxin increased the relative weight of the heart and decreased serum aspartate aminotransferase activity and ochratoxin A increased serum uric acid. The toxicity resulting from the combination of aflatoxin and ochratoxin A was more severe than when either of these mycotoxins were present alone. Addition of HSCAS alone did not alter any of the parameters evaluated. The HSCAS reduced the toxicity of aflatoxin, but had little effect on either the toxicity of ochratoxin A alone or the toxicity resulting from the combination of aflatoxin and ochratoxin A.

Risk assessment to humans of mycotoxins in animal-derived food products.

This paper addresses approaches for assessing potential human health hazards from the presence of natural toxicants, such as mycotoxins, in animal food products. At high levels in feed these mycotoxins may cause loss or illness of farm animals, through development of animal toxicoses, such as aflatoxicosis. At lower levels in feed these mycotoxins may have no apparent effect on livestock production, but their residues and related substances may move up the food chain. This indirect intake of mycotoxins and related substances from the consumption of animal food products may pose a health hazard to humans. These health hazards are compared to the possible health hazards from the direct intake by humans of cereal and other food crops that may contain mycotoxins.