Research at CIIT indicates the plasticizer di(n-butyl)phthalate (DBP) at high doses disrupts a variety of reproductive functions in male rats when exposed in the womb during late gestation, a crucial time window for sexual development. The findings of Dr. Eve Mylchreest and her colleagues are reported in the latest issue of the journal Toxicology and Applied Pharmacology (Vol. 156, 81-95).
A key finding, however, is that the effects are not caused through direct interaction with the androgen, or male sex hormone receptors in cells during this period of sexual differentiation, but through another unknown mechanism. It had previously been suggested that this chemical interacts with hormone receptors.
Overall effects included malformed or missing sexual organs, nondescended testes, and cell proliferation. Abnormal tissue growth, undeveloped prostates, and malformed penises occurred only at the highest exposure levels (500 mg/kg/day).
This study did show an increase in testicular Leydig cell tumors in young adult rats that were exposed to DBP during the last ten days of their motherís pregnancy. This is the first report of Leydig cell tumors in laboratory animals for this group of chemicals and the presence of these tumors in 3-month-old rats is unprecedented for any chemical. They usually appear only in aging rats that have been chronically exposed to a chemical. These rat tumors have a different cellular origin than the most common testicular tumors, raising questions about their human relevance.
In this study, pregnant female rats were fed DBP, flutamide (a positive control known to cause male reproductive developmental effects), or corn oil (the control) daily during the last ten days of pregnancy (gestation day 12 to 21).
The lowest exposure level where effects were noticed was 100 milligrams per kilogram per day. The lowest dosage studied was at least one thousand times higher than the highest reported human exposure level. This study extends the findings of a 1998 CIIT study in which DBP exposure spanned all of gestation and lactation.
Researchers will now focus on larger group sizes with a wider range of dose levels. More work must be done on lab animals and on human exposure to DBP before scientists and regulators have a clear picture on the potential risk to humans from low level exposure to DBP.
CIIT is a scientifically independent, not-for-profit research institute supported primarily by the chemical industry. Its peer-reviewed research is published in critical scientific journals.
Materials provided by Chemical Industry Institute Of Toxicology. Note: Content may be edited for style and length.
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