RESULTS OF A 2-YEAR CHRONIC TOXICITY AND ONCOGENIC STUDY OF RATS INGESTING DIETS CONTAINING 2,4,5-TRICHLOROPHENOXYACETIC ACID (2,4,5-T)

Groups of Sprague-Dawley rats (50 males and 50 females) were maintained on diets supplying 3, 10 or 30 mg 2,4,5-T/kg body weight/day for up to 2 yr, with an interim autopsy (on an additional ten males and ten females per group) after 118-119 days. The highest dose level was associated with some degree of toxicity, including a decrease in body-weight gain and increases in relative kidney weight, in the volume of urine excreted and in the urinary excretion of coprophorphyrin and uroporphyrin, plus slight morphological changes in the kidney, liver and lungs. The kidney changes involved, primarily, the presence of mineralized deposits in the renal pelvis. Parameters not adversely affected by this dose level included death rate, food consumption, the occurrence of palpable masses, haematological indices (red-cell count, haemoglobin, packed cell volume, total and differential white-cell counts, thrombocytes and reticulocytes), the results of routine urine analyses, urinary excretion of creatinine and δ-aminolaevulinic acid, serum-chemistry values (urea nitrogen, glutamic-pyruvic-transaminase and alkaline-phosphatase activities, bilirubin, total protein, albumin and globulin), weights of organs other than the kidneys, tumour incidence and gross and microscopic morphology of all the organ systems examined, with the exception of those mentioned above. At the intermediate dose level (10 mg/kg/day) only minimal effects were noted, primarily an increased incidence of mineralized deposits in the renal pelvis and, in the males and only during the early phase of the study, an increase in urinary excretion of coproporphyrin. At the lower dose level (3 mg/kg/day) there were no changes that were considered to be related to treatment throughout the 2-yr period. Thus, this study revealed no oncogenic response in rats, even when the duration of 2,4,5-T administration extended over most of their lifespan at a dosage high enough to induce toxicity. © 1979.