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The placental and lactational transfer of ochratoxin A (OA) was investigated in a cross-fostering study in rats. Dams were given 50 microg OA(-1) kg body weight by gastric intubations 5 times a week for 2 weeks before mating, during gestation and then 7 days a week during lactation. Neonates from OA-treated dams were cross-fostered at birth to control dams treated with only vehicle. In the same way, neonates from control dams were cross-fostered to OA-treated dams. Treatment with OA did not result in any effects on birth weight or growth development of the pups during the first 21 days of life. There were no effects on milk quality as measured by milk lipids, protein or lactose concentrations, or on milk production, assessed by the mammary gland content of RNA and DNA. A mean milk:blood ratio of approximately 0.6 was found. The dose of OA from milk to the suckling pup at 14 days of age can be calculated to about 50 microg kg(-1) body weight(-1) day, which is similar to the dose given to the dams. Pups exposed to OA only via milk had blood and kidney levels of OA approximately 3 times higher than their dams, indicating a high absorption and/or a low excretion of OA in the sucklings. At 14 days of age the highest blood and kidney levels of OA were found in offspring exposed both via placenta and milk, with the highest contribution from milk. Offspring exposed only via milk had about 4-5 times higher levels of OA in blood and kidney compared to offspring exposed only via placenta. As milk could be a significant source of OA exposure in newborns, adverse health effects resulting from postnatal exposure should be studied and evaluated in the risk assessment of OA.

Effects on the immune system after perinatal exposure to ochratoxin A (OA) were studied in Sprague-Dawley rats after single or repeated exposure of the dams. In a short-term study, dams with litters were given a single dose of OA (0, 10, 50 or 250 micrograms/kg body weight) on day 11 of lactation. The effects on cell numbers in spleen and thymus and on the mitogen responses of lymphocytes were evaluated in the suckling pups on day 14 of lactation. The proliferative response of splenocytes to the T-cell mitogen Concanavalin A (Con A) was significantly stimulated in pups from dams given 10 or 50 micrograms OA/kg body weight as compared to control pups. In addition, proliferation of thymocytes in response to Con A was stimulated in pups from dams exposed to 50 micrograms OA/kg body weight. In a long-term, cross-fostering study comparing pre- and postnatal exposure, half of the dams received 50 micrograms OA/kg body weight 5 days a week by gastric intubation 2 weeks before mating, during gestation and then 7 days a week until weaning. Effects on immune parameters were studied in the pups on day 14 of lactation and at 13 weeks of age. Suppressed mitogenic responses were seen to both lipopolysaccharide (LPS) and Con A in prenatally exposed pups sampled on day 14 of lactation. At 13 weeks the response of splenocytes to LPS was still impaired. The primary antibody response to a viral antigen was also lower in the prenatally exposed pups than in the control pups. These effects on the immune response were not seen in the groups of pups exposed postnatally or both pre- and postnatally, although blood concentrations of OA were higher in these groups at the time of the first sampling. This indicates that the decrease in proliferation and antibody production resulted from prenatal modulation of the immune system. The results show that prenatal exposure to relatively low doses of OA may induce immunosuppression. In contrast, short-term exposure of suckling pups to OA via the milk stimulates the proliferative responses of lymphocytes to polyclonal activation.

A dose-dependent transfer of ochratoxin A into the milk of lactating rats was found after a single oral dose of ochratoxin A, given in the dose levels of 10, 50, and 250-micrograms ochratoxin A/kg body weight by gastric intubation. The milk/blood concentration ratio of ochratoxin A at 24 and 72 h was 0.4 and 0.7, respectively. A linear relationship was found between the concentration of ochratoxin A in the dam's milk and in the blood of the pups at 72 h, as well as in the dam's milk and in the kidneys of the pups. The pup blood/milk concentration ratio of ochratoxin A was approximately 6. At 72 h the sucklings had higher levels of ochratoxin A than their dams in both blood and kidneys. The results show that the concentration of ochratoxin A in milk can be used as an indicator of the continuously administered dose to the suckling.

The toxicokinetic parameters of ochratoxin A in rat following intratracheal administration of 50 ng ochratoxin A/g body weight were studied. The absorption of ochratoxin A from the lungs was very efficient. The elimination pattern of the toxin was studied by the analysis of blood samples. The biological half-life of ochratoxin A was 127 h and the calculated apparent volume of distribution equalled 168 ml/kg. The bioavailability of the toxin was very high, 98%. The plasma clearance of the toxin was 0.92 ml/kg.h.