Controversies in fumonisin mycotoxicology and risk assessment.

Fusarium verticillioides causes several animal diseases and the contamination maize suggests that it could adversely affect human health. The fumonisin B mycotoxins were characterized from the fungal culture material and shown to be the causative principle responsible for the major mycotoxicological effects of the fungus in experimental and farm animals. The main focus was on the toxicological effects in rats and mice, the outcome of which played an important role in setting risk assessment parameters for exposure of the fumonisins to humans. The International Agency for Research on Cancer characterized the fumonisins as Group 2B carcinogens. Several controversial findings regarding the toxicological effects of the culture material of the fungus, the genotoxicity and carcinogenicity of pure fumonisin B(1) (FB(1)) in rats have been reported that should be clarified prior to assessing the risk in humans. The underlying differences between the diets with the high protein levels are likely to sensitize the kidneys to FB(1)-induced toxic and carcinogenic effects. Several other dietary factors, such as plant extracts (antioxidants) and dietary Fe, could either stimulate or inhibit cancer induction of FB(1), which complicates the comparison of toxicological effects in experimental animals. Cognisance should be taken of the modulating role of dietary constituents as it will determine the outcome of toxicological assays and determine the threshold of an adverse effect in a specific target organ to be used in determining risk assessment parameters.

Soil fertility factors in relation to oesophageal cancer risk areas in Transkei, southern Africa.

Soil samples were collected during certain years for the period 1982-89 from high- and low-risk areas for oesophageal cancer in Transkei, southern Africa. These samples were taken either from cultivated soils under maize monoculture, or from uncultivated soils (1989 only) adjacent to the maize fields. Analyses of mineral elements in the soil samples were performed at two independent laboratories. Furthermore, soil and maize leaf samples, from field trials in a high- and a low-risk area for oesophageal cancer were analysed. The results from this study do not agree with those reported previously for Transkei. Cultivated soils in both high- and low-risk areas were found to be highly fertile. The levels of Mn, Ni, Mg, Ca, K and soil pH were significantly higher, and Al, Fe and organic matter significantly lower in the high-risk compared with the low-risk area. Leaf analysis, although not tested statistically, indicated higher levels of Mn K, Ca and Fe, and lower levels of P, in the high-risk area.

Selenium and other mineral elements in populations at risk for esophageal cancer.

The current study tested the hypothesis that deficiencies of certain mineral elements are risk factors for esophageal cancer (EC). In rural blacks living in areas with moderate to high EC incidence rates in southern Africa, the whole blood selenium (Se) levels were found to be significantly (P less than 0.0005) lower (58 to 71 ng/ml) than those of rural and urban populations living in low EC rate areas (114 to 177 ng/ml). No significant differences were found in the plasma levels of the other mineral elements examined, including zinc, copper, and magnesium. Within a high EC rate area occupants of households with previously recorded EC cases had significantly (P less than 0.0025) lower levels of Se (64 ng/ml), but not of other mineral elements, than subjects from households without known cases (77 ng/ml). Mean Se levels of subjects with premalignant or malignant esophageal cytological changes (54 ng/ml) were significantly (P less than 0.0025) lower than those of subjects without such lesions (68 ng/ml). An inverse relationship was found between Se status and the degree of cytologic abnormality. These findings suggest that Se deficiency may play a role in the development of EC. The potential value of whole blood Se determinations and esophageal cytologic examinations in the early detection and of Se supplementation in the prevention of EC merits further investigation.

Photosensitivity in South Africa. II. The experimental production of the ovine hepatogenous photosensitivity disease geeldikkop (Tribulosis ovis) by the simultaneous ingestion of Tribulus terrestris plants and cultures of Pithomyces chartarum containing the mycotoxin sporidesmin.

The mycoflora of toxic pastures were surveyed during a number of outbreaks of ovine hepatogenous photosensitivity in South Africa. Pure cultures of several isolates were dosed to sheep, but only those of Pithomyces chartarum and Myrothecium verrucaria proved to be toxic. Photosensitization was induced in sheep by dosing them with cultures of a P. chartarum isolate (GA10) obtained from Tribulus terrestris plants collected during an outbreak of geeldikkop in the Karoo. Thus for the first time a mechanism whereby T. terrestris plants can contribute to the causation of ovine hepatogenous photosensitivity was demonstrated. When cultures of GA10 equivalent to approximately 0,75--4,0 mg/kg sporidesmin were dosed at Onderstepoort Veterinary Research Institute to Highveld and Karoo sheep on a diet of lucerne, facial eczema was produced. Dosing the same cultures at levels equivalent to c. 1,0 mg/kg of sporidesmin in the Karoo resulted in lesions characteristic of both facial eczema and geeldikkop. Typical hepatic lesions of geeldikkop could be elicited by dosing GA10 at levels equivalent to c. 0,25--0,7 mg/kg of sporidesmin to Karoo sheep grazing on predominantly T. terrestris pastures in the Karoo. In the latter experiment geeldikkop was induced in the sheep on T. terrestris pastures, while those receiving identical doses on veld with little T. terrestris developed facial eczema. Geeldikkop, therefore, can be brought about by the ingestion of T. terrestris plants together with toxic cultures of P. chartarum. The plant appears not only to act as a vehicle for ingestion of spores, but also to interact with sporidesmin to induce lesions typical of geeldikkop, whereas sporidesmin alone results in facial eczema. Indications are that it can enhance the ability of sporidesmin to cause photosensitivity or, possibly, vice versa. The histopathological findings of these experiments are described in detail.