Porcine Nephropathy Induced by Long-Term Ingestion of Ochratoxin A

Abstract

Abstract. Nine pigs were fed crystalline ochratoxin A in their feed at a concentration of about I mg/kg. Three pigs and their controls were killed after 3 months and 6 pigs and controls were killed after 2 years. A decrease of the ratio TmlB..tI1/CI,,. increased urinary glucose excretion and decreased ability to concentrate urine. occurred within a few weeks and aggravated slightly during the 2-year period. Changes in renal structure. characterized by degeneration and atrophy of proximal tubules. interstitial fibrosis and hyalinization of glomeruli, were progressive during time of exposure. but terminal renal failure was not reached. The kidney. liver. muscular and adipose tissue contained 3 to 27 p g ochratoxin A/kg after 3 months of exposure. N o further accumulation of ochratoxin A residue was found after 2 years of exposure.Mycotoxic nephropathy is a naturally occurring disease of pigs and poultry [5, 81. Ochratoxin A, a dihydroisocoumarin derivative linked through its 7 carboxy group to L-P-phenylalanine, is a nephrotoxic mycotoxin of several species belonging to the fungal genera Aspergillus and Penicillium. This compound. occurring in feeds and foods, has been observed as a major disease determinant of porcine and possibly also avian nephropathy [5, 61. Porcine nephropathy similar to that of naturally occurring cases [3, 141 has been reproduced by exposure to ochratoxin A during a 3-to 4-month period [7]. Ochratoxin A has been suggested as a causal determinant of Balkan (endemic) nephropathy [4]. A recent survey indicated that foodborn exposure to ochratoxin A is higher in an endemic area than in nonendemic areas [ 121.

Health risk assessment of ochratoxin A for all age-sex strata in a market economy

“…The most sensitive parameter was a decrease in the maximum tubular excretion ( T M ) of p -aminohippuric acid (PAH) at all dose levels. In a subsequent 2-year study, six pigs per group were exposed to a single dose level of 40 µg OTA kgbw −1 per day (Krogh et al 1979) resulting in a more severe nephropathy at 2 years compared with 14 weeks based on histopathology, decreased urine osmolality, and increased glucose excretion. Thus, a NOAEL or LOAEL could not be derived from this single-dose study.…”

“…Even if OTA were to be regulated as a threshold carcinogen and nephrotoxicity in pigs used as an endpoint, the available 90-day study in pigs (Krogh et al 1974, 1979, see Hazard Identification) has several limitations. Our review of the recent EFSA Opinion (2006) revealed several methodological issues related to the choice of uncertainty factors applied to the endpoint of nephrotoxicity (Table 2).…”

A reassessment of risk associated with dietary intake of ochratoxin A based on a lifetime exposure model

“…Kuiper-Goodman et al (2010) applied an additional uncertainty factor of two to extrapolate the 90-day subchronic study to a chronic study (this is a default that is consistent with other risk-assessment methodologies). However, in other longer term pig studies, such as the follow-up study by Krogh et al (1979), the exposure of pigs to approximately 40 μg/kg body weight/day for up to 2 years led to progressive nephropathy but no renal failure (EFSA, 2006). Hence, the changes in renal function occurring at the lower dose of 8 μg/kg body weight/day in the 90-day study would not have been expected to progress to renal failure should exposure have been continued.…”

“…The lowest observed-effect level of 8 μg/kg body weight/day was determined from a 90-day subchronic study, in groups of 6 to 11 pigs, in which renal enzyme changes, and changes in renal function were noted at all doses (Krogh et al, 1974). In a follow-up study (Krogh et al, 1979), exposure of six pigs to approximately 40 μg/kg body weight/day for 2 years led to progressive nephropathy but not renal failure. One striking difference observed in the kinetics of OTA in the pig, which may explain this species greater sensitivity to OTA is provided by work of Hagelberg et al (1989) who calculated clearance of OTA by renal filtration using glomerular filtration rates and concentrations of free fractions of OTA in plasma.…”

Aflatoksin-Bağlayıcı Lokal Sodyum Bentonitin’in Yumurtacı Tavukların Üretim Performansı Üzerine Etkileri

“…Aflatoxicosis, severely affected the development of broiler as well egg production in layers and produced symptoms like anemia, enlargement of hemorrhagic liver, fat accumulation, kidney paleness and reduced feed uptake [2,3] . Another important mycotoxin in poultry diet is Ochratoxin A (OTA ), which is produced by Aspergillus and Penicillium species of fungi, and have carcinogenic effects especially on kidney and liver [4][5][6] . Lowlevel exposure to OTA leads to reduced feed consumption and increase susceptibility to diseases [7] .…”