Effects of Di(2-Ethylhexyl) Phthalate on the Gonadal Pathophysiology, Sperm Morphology, and Reproductive Performance of Male Rats

Abstract

Dietary exposure of adult male F344 rats to 0, 320, 1250, 5000, or 20,000 ppm DEHP for 60 consecutive days resulted in a dose-dependent reduction in total body, testis, epididymis, and prostate weights at 5000 and 20,000 ppm. Degenerative changes were observed in testis, along with decreased testicular zinc content, reduced epididymal sperm density and motility, and increased occurrence of abnormal sperm at 20,000 ppm. There was a trend towards reduced testosterone and increased luteinizing hormone and follicle stimulating hormone in serum at 5000 and 20,000 ppm. The mean percentage of fertile animals was unchanged and reduction in fertility parameters, although not marked in severity, were correlated with gonadal effects. Average litter size was reduced at 20,000 ppm, but initial pup weights and growth were unaffected. There were no grossly observed abnormalities in the offspring and the rate of neonatal deaths was similar in control and DEHP treated groups. Characteristic toxicity manifestations of DEHP included dose-dependent enlargement of liver and reduced sperm triglycerides and cholesterol. Additionally, serum albumin and total proteins were dose dependently increased upon treatment with DEHP. Cessation of exposure to DEHP initiated partial to complete recovery from toxicity in most cases. The magnitude of recovery were variable with that of the gonads being slower than other systems. These data suggest a lack of reproductive dysfunction in F344 male rats at DEHP doses below 20,000 ppm which produced measurable testicular degeneration and afflicted epididymal sperm morphology under the present experimental conditions.

Distribution of phthalate esters in the groundwater of Jianghan plain, Hubei, China

“…Several PAEs are carcinogenic in animal models (Huber et al, 1996). In addition, some PAEs and their metabolic products act functionally as antiandrogens during the prenatal period (Mylchreest et al, 1998;Moore et al, 2001) and cause reproductive and developmental toxicities in animals (Agarwal et al, 1986). Recent investigations have shown that several PAEs are environmental hormones (Kambia et al, 2001).…”

Analysis of human urine for fifteen phthalate metabolites using automated solid-phase extraction

“…Some phthalates and their monoester metabolites can cause reproductive and developmental toxicities in animals [9][10][11][12], but little is known about the effects of phthalate exposure on humans. Information on the concentration of phthalates in people is essential to understand the human exposure to phthalates.…”

Quantification of 22 phthalate metabolites in human urine☆

“…Several phthalates are known to cause carcinogenic, reproductive, and development toxicities in animals [2][3][4][5][6][7][8]. Despite an emerging number of studies in this field [9][10][11][12], data on the effects of phthalate exposure in humans are still limited.…”