IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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IARC MONOGRAPHS VOLUME 82
observed in horses and ponies after ingestion of feeds naturally contaminated with fumonisins
at low concentrations (Wilson et al., 1992; Ross et al., 1993). The development of
brain lesions in the absence of major liver lesions does not preclude a contribution of biochemical
dysfunction in non-brain tissue to the development of brain lesions. Length of
exposure, level of contamination, individual animal differences, previous exposure or
pre-existing liver impairment may all contribute to the appearance of the clinical disease
(Ross et al., 1993).
The lowest dietary dose observed to induce ELEM was 22 mg/kg fumonisin B 1
in a diet formulated with naturally contaminated maize screenings: one pony died of
ELEM after consumption of contaminated diet for 235 days, of which the final 55 days’
diet contained 22 ppm fumonisin B 1 (Wilson et al., 1992). Analysis of feeds from
confirmed cases of ELEM indicated that consumption of feed with a fumonisin B 1 concentration
greater than 10 mg/kg diet is associated with increased risk of development of
ELEM, whereas a concentration less than 6 mg/kg is not (Ross et al., 1994). The minimum
toxic dose of pure fumonisins is unknown.
In swine, fumonisin B 1 causes damage to the liver, lungs and cardiovascular and
immune systems. Liver lesions have been induced with fumonisin-contaminated maize
screenings at 1.1 mg/kg per day (fumonisins B 1 and B 2; 17 mg/kg fumonisin B 1 and
6 mg/kg fumonisin B 2 in the diet). Intravenous exposures resulted in changes similar to
those recorded in rodents including necrosis and cell proliferation (Motelin et al., 1994;
Haschek et al., 2001). When pure fumonisin B 1 was fed to Yorkshire swine at dietary
levels of 0.1, 1 or 10 mg/kg (0.005, 0.052 or 0.496 mg/kg bw), apart from reduced organ
weights (pancreas, adrenals), no histopathological signs of organ damage were observed.
There were changes in sphingolipid ratios in lung, liver and kidney at the highest dose,
as well as increased serum cholesterol (Rotter et al., 1996). Fumonisin B 1 given to young
adult swine at several doses up to 1 mg/kg in the diet resulted in changes in serum cholesterol
and in altered carcass fat distribution at 0.05 mg/kg bw (Rotter et al., 1997).
Lung oedema occurs in pigs following very high fumonisin B 1 exposure (≥
100 ppm in diet, or ≥ 16 mg/kg bw per day). Clinical signs of lung oedema typically
occur 2–7 days after exposure, and usually include dyspnoea, weakness, cyanosis and
death (Osweiler et al., 1992; Haschek et al., 2001). At necropsy, the animals exhibit
varying degrees of interstitial and interlobular oedema, with pulmonary oedema and
hydrothorax, with varying amounts of clear yellow fluid accumulating in the pleural
cavity (Colvin & Harrison, 1992; Colvin et al., 1993). Fumonisin B 1 is believed to be a
negative osmotropic agent causing decreased cardiac contractility. It has been hypothesized
that the cardiovascular alterations are a consequence of sphingosine-induced
inhibition of L-type calcium channels. Pulmonary oedema results from left-sided heart
failure (Smith et al., 1996, 2000; Haschek et al., 2001). Porcine pulmonary oedema was
produced within 3–4 days after pigs started consuming a diet of culture material that
provided 20 mg/kg bw fumonisin B 1 per day (Smith et al., 1999). There are no published
studies on pulmonary oedema induced by oral exposure to pure fumonisin B 1.