Endocrine disrupting chemicals, 4-nonylphenol, bisphenol A and butyl benzyl phthalate, impair metabolism of estradiol in male and female rats as assessed by levels of 15α-hydroxyestrogens and catechol estrogens in urine.

Abstract

Bisphenol A (BPA), 4-nonylphenol (NP) and butyl benzyl phthalate (BBP), termed endocrine-disrupting chemicals, are known to mimic estrogen activity. The effects of these chemicals on 17β-estradiol (E2 ) metabolism in vivo in rats were examined. Male and female rats were given NP (250mg kg-1 day-1 ), BPA (250μg kg-1 day-1 ) or BBP (500mg kg-1 day-1 ) by gavage for 14days, followed by a single intraperitoneal injection of E2 (5mg kg-1 ) on the final day. The urinary excretion over 72hours of 2-hydroxyestrone 1-N-acetylcysteine thioether, 2-hydroxyestrone 4-N-acetylcysteine thioether, 4-hydroxyestrone 2-N-acetylcysteine thioether, 2-hydroxy-17β-estradiol (2-OHE2 ), 2-hydroxyestrone (2-OHE1 ), 4-hydroxy-17β-estradiol, 4-hydroxyestrone, 15α-hydroxyestriol (E4 ), 15α-hydroxy-17β-estradiol and 15α-hydroxyestrone was measured. Increases in urinary excretion of 2-OHE1 and decreases in E4 were observed in males treated with NP or BBP. Decreases in urinary excretion of 2-OHE2 and E4 were observed in males treated with BPA. Decreases in urinary excretion of 2-OHE1 and 2-OHE2 were observed in females treated with BBP. Normalized liver and weights were increased in both sexes treated with NP or BBP. Histologic observations revealed marked changes in the distal tubules and collecting ducts in the kidneys of rats exposed to NP and BBP, and hypertrophy in the hepatocytes of the centrilobular zone of the liver. No BPA-related effects on organ weight and on liver or kidney histopathology were found. These results suggest that the 14day oral dosing of NP and BBP disrupted E2 metabolism, resulting from marked morphological and functional alterations in the liver and kidneys. In addition, BPA could induce metabolic and endocrine disruption.