PFOA slows breast development in mice exposed via mom.

Jan 29, 2009

White SS, K Kayoko, LT Jia, BJ Basden, AM Calafat, EP Hines, JP Stanko, CJ Wolf, BD Abbott, SF Fenton.  2008.  Effects of perfluorooctanoic acid on mouse mammary gland development and differentiation resulting from cross-foster and restricted gestational exposuresReproductive Toxicology doi:10.1016/j.reprotox.2008.11.054.




2009-0128pizzagrease
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Breast gland development is delayed in mice that were exposed for only a short time through their mothers -- during late pregnancy or while nursing -- to a now widely used chemical found in nonstick cookware and food packaging. The results show that even a brief exposure during a critical time of development can lead to long-term effects on the developing mammary gland.  It is important to know when chemicals do the most harm so steps can be taken to limit exposures and reduce associated health impacts.

 

 

Context

Perfluorinated compounds (PFCs) are useful industrial chemicals due to their oil- and water-repelling properties. They have many commercial applications as surfactants and surface protectors (e.g., Teflon™ by DuPont), paper and textile coatings, polishes, food packaging (e.g., microwave popcorn bags) and fire-retardant foams.

Perfluorooctanoic acid (PFOA) is a type of PFC. PFOA is commonly used in and can be a byproduct of the manufacture of commercial PFCs.

In the past decade, as PFOA's use has increased, so has its levels in the environment and in people. Some researchers are becoming increasingly alarmed as the pollutant spreads, yet its health effects remain unknown.

Nearly all Americans have PFOA and related chemicals in their bodies. They are commonly found in people around the world. On average, levels in human blood are relatively low, ranging from about 4 to 7 parts per billion (ppb).

PFOA can be rapidly absorbed through eating, drinking, breathing and touching. How long it stays in the body varies. In humans, the half-life -- the time it takes for half of the chemical to breakdown -- is estimated to be about 4 years. The time it stays in some laboratory animals is considerably less -- from just hours to days.

Children may be especially susceptible to exposure, because they crawl, play on floors and mouth hands, toys and other items. Their behaviors put them in almost constant contact with PFC treated items, such as chemically-treated stain-resistant carpet, clothes and food packaging. Also, a younger's rapidly developing body and mind leave them vulnerable to pollutants. 

An expanding number of animal and human studies link PFOA to many health effects. The very persistent chemical can contribute to thyroid problems, immune changes and cancer (testicular, liver and pancreatic) in laboratory animals. People exposed to PFOA at work may be at higher risk for pancreas, testis and prostate cancers.

In mice, breast tissue develops abnormally if exposed in the womb. Offspring were most vulnerable during the second and third trimesters (White 2007). This current study -- by the same researchers at US Environmental Protection Agency -- further defines the time when PFOA affects the mammary gland.

In early 2006, the eight manufacturers that make PFOA agreed to remove the chemical from products by the year 2015 (US EPA 2006). However, even as manufacturing is phased out, PFOAs will remain. The chemical does not break down easily; it is a byproduct of PFC manufacturing; and it is produced in animals and people during metabolism of other PFCs.

What did they do?

Mice were exposed to PFOA during three different prebirth periods to pinpoint the time when the chemical alters mammary gland development. 

In the first two experiments, pregnant female mice were given PFOA (up to 5 milligrams/kilograms body weight) orally either throughout pregnancy (experiment 1) or for only the second and third trimesters (experiment 2).  Control mice were given plain water. 

After birth, the pups from one mother were switched with pups from another mother, who then served as a foster parent (cross-fostering).  This switch-around resulted in four exposure scenarios:  no exposure to PFOA, exposure in the womb only, exposure via foster mother's milk only or exposure in the womb and through milk. 

The researchers examined the impact of PFOA on breast development in the offspring after they matured to adults (experiment 1) or as newborns (experiment 2). They assessed growth delays by the presence or absence of ducts, tissues and glands at the times when they should form. Longer delays and reduced growth indicated more severe effects.

In the third experiment, the researchers tested specific windows of PFOA exposure.  They exposed the pregnant mice during different intervals of late pregnancy, including a very short 2-day exposure. Mammary gland development in the offspring was evaluated at mid-life (22 to 62 days after-birth) and at an older age (18 months).

What did they find?

All offspring exposed to 5 mg/kg PFOA -- whether in the womb or via mother's milk or both -- had impaired mammary gland development by adulthood.  In fact, the cross-foster experiments showed that one route of PFOA exposure was no worse on the pups than another route.

Another key finding was that all offpsring exposed to PFOA in the womb showed delays in mammary gland development as early as the first day after birth.  The breast development changes persisted well into adulthood after levels of PFOA in the blood had returned to levels similar to those in the control mice.  

Finally, offspring that were exposed to PFOA for brief periods during very late pregnancy or early life were particularly susceptible to the developmental toxicity of PFOA.  Indeed, a very short exposure (at least 12 hours) via nursing at a critical time of rapid gland changes was sufficient to adversely impact breast development. 

What does it mean?

The results of this study suggest that brief exposure to PFOA in early life -- especially during critical periods of development -- may lead to permanent changes in mammary gland structure. The same is also true for other environmental agents, such as dioxin (Fenton 2006).

How PFOA causes these changes in breast development is not known, but the authors are continuing this work and looking into the possible role of a signaling molecule called PPAR alpha.

The measured concentrations of PFOA in the offspring were about 4 times higher than has been reported for individuals in highly exposed communities (2,000 nanograms/mililiter (ng/ml) compared to around 500 ng/ml). They are much higher than the general population (average about 5 ng/ml).

Therefore, it is not known whether human exposure to PFOA in the womb is likely to impact early breast development in children or a woman's ability to breast feed later in life.


Resources

Environmental Working Group. 2003. PFCs: a family of chemicals that contaminate the planet.

Fenton S. 2006.  Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences. Endocrinology (6 Suppl):S18-24

US EPA. 2006. 100 percent Participation and Commitment in EPA's PFOA Stewardship Program. Press release, March 2, 2006.

US EPA. 2007. Perfluorooctanoic Acid (PFOA).

White SS, AM Calafat, K Kuklenyik, L Villanueva, RD Zehr, L Helfant, MJ Strynar, AB Lindstrom, JR Thibodeaux, C Wood, and SE Fenton. 2007. Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring. Toxicological Science 96: 133-144.

 
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