National Toxicology Program

National Toxicology Program

Abstract for IMM96016 - Patulin (CASRN 149-29-1)

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

The Immunotoxicity of Patulin
(CAS No. 149-29-1) in Female Fischer 344 Rats

NTP Report Number IMM96016


Patulin (PTL) 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 (NTP) 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 Fischer 344 rats. The animals were exposed to PTL at dose levels of 1.28, 2.56, and 5.12 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 20 August 1996 to 20 December 1996.

Executive Summary Table 1 (ES-1) shows a summary of the standard toxicology and immunology studies for patulin. 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 liver, spleen, lungs or thymus weights. PTL exposure at the high dose level, 5.12 mg/kg, produced a decrease in kidney weight that reached the level of statistical significance when compared to the vehicle controls. There was a 10% decrease in absolute weight, an 8% decrease in relative weight, i.e. percent body weight, and a 10% decrease in organ-to-brain ratio. The erythrocyte and leukocyte counts, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets and reticulocytes were unaffected by PTL. No effect was observed on the percentage or absolute numbers of lymphocytes, neutrophils or eosinophils in the leukocyte differential.

A decrease in spleen cell number was observed at the high dose level, and splenic phenotypes paralleled the decrease in spleen cell number at the high dose with the exception of total T cells which was statistically decreased when evaluated as either percent values or absolute values. No significant differences were observed in the antibody-forming cell response to the T-dependent antigen sRBC when compared to the vehicle-exposed animals. Furthermore, PTL exposure had no effect on the anti-sRBC serum titer or basal total IgM and IgG antibody levels. When compared to the vehicle-exposed animals, there was a 22% decrease at the low dose (1.28 mg/kg) level of PTL in the 200:1 effector:target ratio for the natural killer (NK) cell activity. However, this decrease in NK activity at one dose and a single effector-to-target ratio, and in the absence of other effects is not considered to be biologically meaningful. Aflatoxin B1, a known immunosuppressive mycotoxin, was used as a comparative control and produced the anticipated immunological and toxicological changes in the study.

In conclusion, under the experimental conditions of the study, patulin did not adversely affect the immune system of female Fischer 344 at doses levels up to and including 5.12 mg/kg when administered by oral gavage for 28 days.

Table ES-1
Parameter Results Maximum Effect Dose Comments
Body Weight        
    Day 8 No Effect      
    Day 15 No Effect      
    Day 22 No Effect      
    Day 29 No Effect      
Weight Changes        
    Day 8-1 No Effect      
    Day 15-1 No Effect      
    Day 22-1 No Effect      
    Day 29-1 No Effect      
  Gross Pathology No Effect      
  Organ Weights        
    Liver No Effect      
    Spleen No Effect      
    Lungs No Effect      
    Thymus No Effect      
    Kidney Decrease 10% 5.12 mg/kg  
  RBCs No Effect      
    Hemoglobin No Effect      
    Hematocrit No Effect      
    MCV No Effect      
    MCH No Effect      
    MCHC No Effect      
  Reticulocytes No Effect      
  Platelets No Effect      
  Leukocytes No Effect      
    Lymphocytes No Effect      
    Neutrophils No Effect      
    Eosinophils No Effect      
Surface Markers (Absolute Values)
    OX-33+ Decrease 17% 5.12 mg/kg Absolute Values Only
    OX-19+ Decrease 25% 5.12 mg/kg  
    OX-38+ Decrease 17% 5.12 mg/kg Absolute Values Only
    OX-8+NK- Decrease 20% 5.12 mg/kg Absolute Values Only
    NKR-P1A+OX-8+ No Effect      
    Mac-1+HIS36+ No Effect      
IgM Humoral Immune Response to Sheep Erythrocytes
    IgM AFC to sRBC No Effect      
    Serum IgM Titers No Effect      
    Basal IgM & IgG No Effect      
NK Cell Activity
    200:1 E:T Ratio Decrease 22% 1.28 mg/kg  
    LU 107 Cells No Effect      
    LU/Spleen No Effect      

Report Date: June 2004

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