Mono-2-ethylhexyl phthalate, a metabolite of di-(2-ethylhexyl) phthalate, causally linked to testicular atrophy in rats.
Acute testicular atrophy results when appropriate dosages of di-(2-ethylhexyl) phthalate (DEHP) or its hydrolysis product mono-2-ethylhexyl phthalate (MEHP) are given to male rats. Events thought to be involved in this pathological effect also occur in cultures of testicular cells in vitro, but require MEHP rather than DEHP. Primary cultures of hepatocytes, Sertoli cells, and Leydig cells were incubated with 14C-labeled MEHP [8 microM] for up to 24 hr. No significant reduction in viability was produced under these conditions. In contrast to the hepatocytes, which extensively metabolized MEHP to a variety of products in 1 hr, the testicular cell cultures were apparently unable to metabolize MEHP (beyond a slight hydrolysis to phthalic acid by Sertoli cells) in 18-24 hr. MEHP was efficiently taken up by hepatocytes, but much less so by testicular cells. These results, combined with related observations from the literature, support the hypothesis that MEHP itself is the metabolite of DEHP responsible for testicular atrophy in rats.
National Institute of Environmental Health Sciences, Laboratory of Molecular Biophysics, Research Triangle Park, North Carolina.
P W
PW
Albro
R E
RE
Chapin
J T
JT
Corbett
J
J
Schroeder
J L
JL
Phelps
D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000378:metabolism; D002478:Cells, Cultured; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity*; D006868:Hydrolysis; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010795:Phthalic Acids / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D010795:Phthalic Acids; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate