The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Patulin is a naturally occurring mycotoxin potentially found in apple juice at levels that have caused concern for some populations of people, especially young children. The National Toxicology Program requested that a dose range-finding study be performed in order to establish the potential effects of PTL on the immune system and to determine doses that could be used in a full immunotoxicology study. These studies were conducted in female B6C3F1 mice. The animals were exposed to PTL at dose levels of 0.08, 0.16, 0.32, 0.64, 1.28, and 2.56 mg/kg for 28 days by the oral gavage route. PTL was prepared weekly in sterile distilled water. The in-life phase of these studies was carried out between 26 April 1996 and 30 May 1996.
In this study, no effects were observed with the PTL-exposed animals on either body weight or body weight gain compared to the vehicle control animals exposed to sterile water. Furthermore, no effect was observed on spleen, liver, lungs, thymus or kidney weights. The only organ weight to show a change was absolute brain weight which was increased 16% at the 0.64 mg/kg dose level. The erythrocyte count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentrationMCHC, platelets, and reticulocytes were unaffected by PTL. Leukocyte counts were decreased by 30% at the 1.28 mg/kg dose level and 32% at the 2.56 mg/kg dose level. No effect was observed on the percentage of lymphocytes, neutrophils or eosinophils in the leukocyte differential. However, when lymphocytes were evaluated as absolute numbers, a 33% statistically significant decrease was observed in each of the two highest dose levels. No significant differences were observed in the antibody-forming cell response to the T-dependent antigen sheep red blood cells when compared to the vehicle-exposed animals. Furthermore, PTL exposure had no effect on the anti-sRBC serum titer. The effects of PTL on the MLR and NK activity were only evaluated at the highest dose level of 2.56 mg/kg. When compared to the vehicle-exposed animals, no effects were observed on either the mixed leukocyte response or natural killer cell activity.
In conclusion, based on the leukocyte results, the no observable effect level for patulin was 0.64 mg/kg. However, based on the lack of effects on the functional assays, under the experimental conditions of this protocol, patulin was not immunosuppressive at doses levels at or below 2.56 mg/kg.