PROMEC Unit

Research highlights

• Fumonisins, carcinogenic mycotoxins produced by F. verticillioides in maize, were first isolated in 1988 at PROMEC and characterised in collaboration with the CSIR. 
• Analytical standards of the fumonisins are marketed on a worldwide basis.
• Fumonisin B1 was shown to be the causative factor of equine leukoencephalomalacia, a neurotoxic disease of horses which causes economic losses world-wide, especially in the USA. This work was done in collaboration with the Onderstepoort Veterinary Research Institute.
• Fumonisin B1 was shown to be hepatocarcinogenic in rats in 1991. 
• Internationally validated analytical methods were developed to assess contamination of foods and feeds with fumonisins.
• High levels of fumonisins were shown to occur in home-grown maize consumed as the staple diet by people at high risk for Oesophageal Cancer (OC) in the Transkei region of South Africa. 
• Fumonisins have been found in human hair from residents of the Transkei region.
• Risk assessment parameters for fumonisins, i.e. the tolerable daily intake (TDI) for fumonisins in humans, and probable daily intake (PDI) profiles of different population groups were established for the first time by scientists at the PROMEC Unit. The results show that millions of South Africans are exposed to fumonisin levels in maize above the calculated TDI value.
• Data generated by PROMEC formed the basis of the evaluation by the International Agency for Research on Cancer (IARC) of the “toxins produced by F. moniliforme”, and subsequently of fumonisin B1, as Group 2B carcinogens, i.e. possibly carcinogenic to humans.
• Scientists from the PROMEC Unit participated in the 56th Meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the Working Group of the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 
• A CANSA/MRC Consortium for Oesophageal Cancer Research has been established in collaboration with several research institutions and universities with the aim of integrating different approaches to the investigation of OC development, i.e. from Demography to DNA.
• Major contributions by the PROMEC Unit to research on Oesophageal Cancer in the Transkei include the following:
• Cancer registry has provided important information on the temporal and spatial distribution of Oesophageal Cancer in Transkei and revealed increases in incidence rates in both males and females in some areas.
• An early detection method for Oesophageal Cancer by means of oesophageal cytology has been investigated and may become the oesophageal equivalent of the Pap smear for the cervix.
• Extremely high incidences of mycotoxigenic fungi and levels of the carcinogenic fumonisin mycotoxins have been detected in home-grown maize consumed as the staple diet by Transkeians at high risk for Oesophageal Cancer.
• Molecular epidemiological studies suggest specific markers of Oesophageal Cancer in Transkei that may represent the signature of a specific carcinogen.
• The research achievements of the PROMEC Unit have been widely acknowledged nationally and internationally by invitations to write books and chapters for books, present plenary lectures at conferences, serve on international committees and editorial boards, review manuscripts for local and international journals, act as study leaders, promotors and external examiners for post-graduate students and by awards for excellence in science. Some recent examples include the invitation of Dr WCA Gelderblom and Dr GS Shephard by the WHO and FAO, respectively, to participate in the 56th JECFA meeting in Geneva, February 2001; the award of US $10 000 by MONSANTO in February 2001 to PROMEC “because you and your staff are recognised as world leaders in corn mycotoxin research”; the allocation of funds to Prof WFO Marasas under the Agreement on Scientific Collaboration between the Peoples Republic of China and South Africa to facilitate exchange visits to South Africa by five distinguished Chinese scientists and to China by six South African researchers on oesophageal cancer, and many other examples mentioned in this document; Dr HF Vismer was awarded substancial funding from several International Organisations, including the International Society for Human and Animal Mycology and the European Confederation of Medical Mycology as Conference Chairperson to organise the 2nd Pan African Medical Mycology Society (PAMMS) Conference in Cape Town in 2008.
• The Science, Engineering and Technology Institutions (SETI) Review of the Medical Research Council (1998) evaluated PROMEC as an internationally recognised research group and one of the best Programmes in the MRC according to Dr MW Makgoba (Opening of the PROMEC Liquid Chromatography - Mass Spectrometry Facility, 16 April 1998) A grant from the Welcome Trust of R1 300 000 was received to establish this facility.
• Collaboration with other developing countries in Africa (Benin, Cameroon, Ghana, Mali and Nigeria), Latin America (Brazil) and Asia (Iran) has been established in order to investigate mycotoxigenic fungi and mycotoxin contamination levels in essential commodities in these countries.
• A survey of South African wines has concluded that ochratoxin A contamination levels are low and well within the proposed EU legislated limit of 2 µg/L.
• Maize consumption levels by the population in the Centane and Bizana magisterial districts of the former Transkei has been determined and combined with fumonisin contamination levels to yield the first comprehensive assessment of the distribution of fumonisin exposure in these areas.
• A new thin-layer chromatographic method for the determination of fumonisin B1 has been developed as part of an International Atomic Energy Agency (IAEA) project, which involved the PROMEC Unit as coordinator of a consortium of 18 laboratories in both developed and developing countries.
• Interactive associations between fumonisin contamination (mg/kg maize) and maize intake profiles (g/60 kg person/day) yielded the Probable Daily Intake (PDI; µg FB/kg body weight/day) for fumonisins. The Provisional Maximum Tolerable Daily Intake (PMTDI) were calculated based on nephrotoxic effects (2 µg FB/kg body weight/day) as set forward by the JECFA (WHO, 2002) or hepatocarcinogenic effects (0.8 µg FB/kg body weight/day) as proposed by Gelderblom et al., 1996 [In Fumonsins in Food, L.S. Jackson, J.W. De Vries, L.B. Bullerman (Eds) Plenum, New York, NY. pp 279-296]. (see Table below)

FB = Fumonisin B mycotoxins;
White areas: Daily FB intake levels fall below the 0.8 µg PMTDI for hepatocarcinogenicity;
Lightly shaded areas: Daily FB intake levels fall within the 0.8 µg PMTDI for hepatocarcinogenicity;
Medium shaded areas: Daily FB intake levels fall below the 2 µg PMTDI for nephrotoxicity;
Dark shaded areas: Daily FB intake levels fall above the 2 µg PMTDI for nephrotoxicity.