A little known 'super-phthalate' packs a big punch to males, a rat study finds.

What did they do?

Researchers from the U.S. Environmental Protection Agency (EPA) looked at whether prenatal exposure to DPeP could affect the reproductive development of male rats and compared its potency to better-studied phthalates – such as DEHP. 

Pregnant rats were fed DPeP at critical time points in their pregnancies. Their male offspring were examined both as fetuses and after birth to see whether the chemical affected their reproductive development.

One group of moms was fed DPeP only on day 17 of their pregnancies, when fetal testosterone production is just starting. To look at the effects of different doses, the researchers gave the rats 0, 300, 600, 900 or 1,200 milligrams of DPeP per kilogram of body weight per day (mg/kg/day). The researchers then examined the rat fetuses six hours later to see whether there were any effects on testosterone production.

In a second experiment, another group of rats received daily doses of DPeP (0, 11, 33, 100 or 300 mg/kg) from days 14 - 18 of their pregnancies. At the end of that period, the researchers looked at whether the male fetuses’ testicular development – including gene activity – was impacted by DPeP.

In a final experiment, the researchers fed rats DPeP (0, 11, 33, 100 or 300 mg/kg) daily from day 8 - 18 of their pregnancies, the entire period during which male rats’ reproductive development is considered vulnerable to phthalates. The male offspring were examined two days after birth for genital development and nipple retention. Testosterone is needed for normal development in both areas, which are known to be altered by some phthalates, such as DEHP.

What did they find?

In the first experiment, the researchers found a significant reduction in fetal testosterone production within five hours after the moms received a single dose of DPeP (of 300 mg/kg of body weight or higher) on day 17 of pregnancy.

When moms were fed DPeP over a five-day period, testosterone production in the fetuses decreased with DPeP doses higher than 33 mg/kg/day. Gene activity in three key genes involved in testosterone production was reduced in fetal testicular tissue at DPeP doses of 100 mg/kg/day and higher.

The longer, 11-day prenatal exposure to DPeP affected the males’ genitals and nipple formation. In particular, genital development – particularly anogenital distance (AGD) – was affected at doses of 100 mg/kg/day or greater, while male nipples were retained at doses of 300 mg/kg/day or greater.

What does it mean?

The results provide strong evidence that DPeP – a little known and understudied phthalate – may actually pose a greater risk to the developing male reproductive system than the better-known DEHP. DPeP was eight times more potent in reducing testosterone production, 3 - 6 times more potent in blocking gene activity, and 2 - 3 times more potent in causing male genital abnormalities.

Rats share many developmental similarities with humans, so there is good reason to think that prenatal exposure to DPeP would have similar effects on human male reproductive development. In both species, testosterone production during certain critical fetal periods is needed for the reproductive system to develop in characteristically masculine ways. 

The study is important because it provides solid information about how prebirth exposure to different doses of DPeP affect male reproductive development. The authors have filled in data gaps that will help determine whether it, too, might warrant government regulation in the future. Several other less potent phthalate compounds have been identified for stringent regulatory actions by the U.S. Environmental Protection Agency Office of Chemical Safety and Pollution Prevention.

When exposed through mothers during a critical period of development (day 17 of pregnancy in the rat), DPeP rapidly lowered testosterone production in male fetuses and effectively suppressed the activity of genes that are involved in that production. This means that even very brief exposure to this potent phthalate could derail normal development.

DPeP exposure caused many inter-related changes in the male offspring: suppressed gene activity, altered genital development, retained nipples and reduced testosterone levels. Testosterone production was particularly sensitive to DPeP exposure. Normal testosterone levels are essential for many aspects of fetal development, including the reproductive system, the brain and metabolism. Gene activity, nipple retention and genital formation were noticeably affected only at higher levels.

So little research has been done on DPeP that it is unknown how it might affect humans or even what levels people are typically exposed to in their daily lives. It is similarly unknown how much DPeP is used or produced in the U.S. each year (PDF). One study found detectable quantities of DPeP in the urine of 29 percent of people studied, which suggests that further research is greatly needed to determine whether DPeP is as potentially dangerous in humans as it appears to be in rats.