Page 1080 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1012 SECTION | XV Mycotoxins

VetBooks.ir (Kellerman et al., 1972). Marasas et al. (1976) then weight for 28 days in this study did not develop neuro-
logic signs. Purified fumonisin B 1 has also been adminis-
produced a batch of culture material using a strain of
tered orally in other studies (1.25 or 2.5 mg fumonisin
F. verticillioides from an outbreak of leukoencephaloma-
lacia to produce liver damage and neurologic disease in a B 1 /kg of body weight, PO, q24h), producing mild edema
horse. It was then concluded that both hepatic disease and of the brain stem and hepatic disease in 11 12 days in
ELEM were manifestations of the same toxicosis, with two horses. In a subsequent study, animals were fed
different clinical syndromes occurring depending on toxin 0.6 4.0 mg fumonisin B 1 /kg of body weight, PO, q 24 h
dose and length of exposure. Following the isolation and for 33 or 35 days, producing hepatotoxicity and neuro-
purification of FB 1 in the late 1980s, ELEM was logic signs starting on days 22 and 24 in two weanling
experimentally induced by the administration of purified horses (Kellerman et al., 1990).
toxin (Kellerman et al., 1990; Marasas et al., 1988). Doses of fumonisin reported from naturally occurring
cases of fumonisin have varied (Table 71.2). One field
report calculated that the ingestion of 0.6 2.1 mg fumo-
Spontaneous and Experimental Fumonisin nisin B 1 /kg of body weight would induced ELEM in
24 28 days (Wilson et al., 1990b). Another study found
Toxicosis in Horses
that leukoencephalomalacia was associated with ingestion
Since the discovery of fumonisin as the causative agent of of feed containing fumonisin B 1 concentrations greater
ELEM, many more disease outbreaks associated with the than 10 ppm, and concluded that feed with fumonisin B 1
feeding of corn have been reported on virtually all conti- concentrations greater than 10 ppm was not safe to be fed
nents of the world (Bailly et al., 1996; Bela and Endre, to horses (Ross et al., 1991).
1996; Binkerd et al., 1993; Cerrillo et al., 1996; Christley
et al., 1993; Giannitti et al., 2011; Jovanovi´ c et al., 2015; Neurologic and Hepatic Effects in Horses
Rosiles et al., 1998; Ross et al., 1991, 1993; Uhlinger,
1991; Wilkins et al., 1994; Wilson et al., 1990a). Purified Several reports have considered ELEM and hepatotoxicity
fumonisin B 1 has induced ELEM when administered to be two separate syndromes associated with fumonisin
orally (Kellerman et al., 1990) and intravenously toxicity in horses, with the terms “classic neurotoxic syn-
(Foreman et al., 2004; Marasas et al., 1988; Laurent et al., drome” and “hepatic syndrome” being used (McCue,
1989). Purified fumonisin B 2 has also induced ELEM 1989). However it appears more likely these are not true
when given orally (Ross et al., 1994). Fumonisin B 1 is “distinct” syndromes but are related to the concentration
considered to be the primary cause of ELEM however, as of fumonisin in the feed, the duration of toxin consump-
fumonisin B 2 is usually present in concentrations that are tion, and the tolerance of the individual horse to fumoni-
20% 40% of fumonisin B 1 (Ross et al., 1991). Although sin. In some outbreaks, horses have died from ELEM
ELEM has occurred in horses eating commercial feed- while other horses have died from hepatotoxicity, and
stuffs (Ross et al., 1991; Wilson et al., 1990b), the feeding occasionally individual horses exhibiting both neurologic
of corn screenings has been more frequently associated and hepatic signs have been described. Reported clinical
with ELEM, because fumonisin concentrations are much signs associated with hepatic disease include icterus,
higher in screenings than in whole kernels of corn mucous membrane petechiae, and swelling of the lips or
(Binkerd et al., 1993). Fumonisin B 1 also appears to sur- muzzle (Ross et al., 1993; Uhlinger, 1991).
vive the pelleting process for equine feeds (Ross et al., Ross et al. (1993) described an experimental study
1991). where one horse died acutely with “mild encephalopathy
Leukoencephalomalacia has been reproduced with and hepatic necrosis” after 9 days of fumonisin exposure
intravenous administration of fumonisin B 1 in three sepa- whereas two other horses died after 75 and 78 days of
rate studies (Foreman et al., 2004; Laurent et al., 1989; ELEM. The horse that died on day 9 showed neurologic
Marasas et al., 1988). Marasas et al. (1988) administered signs prior to death (“visual impairment, mild ataxia, and
0.125 mg fumonisin B 1 /kg of body weight, IV, q24h, slight head tremors”) and had histologic evidence of leu-
which produced ELEM in 9 days. Laurent et al. (1989) koencephalomalacia at necropsy, however his death was
administered 0.1 mg fumonisin B 1 /kg of body weight, IV, primarily attributed to hepatotoxicity. This study lead to a
q24h for 16 days followed by 0.2 mg/kg/day for 2 addi- common generalization that high doses of fumonisin were
tional days. Leukoencephalomalacia was induced in 18 likely to induce hepatotoxicity, whereas lower doses of
days. Foreman et al. (2004) administered 0.05, 0.1 or toxin over a longer period of time were necessary to
0.2 mg fumonisin B 1 /kg of body weight IV q24h to 10 induce ELEM (McCue, 1989; Plumlee and Galey, 1994).
horses and all developed neurologic signs and were eutha- However in other experimental studies, intravenous
nized between days 4 and 12 of the study. In contrast, administration of fumonisin B 1 induced ELEM in 9 days
horses dosed with 0.01 mg fumonisin B 1 /kg of body (Marasas et al., 1988) and 18 days (Laurent et al., 1989).