A strange catastrophe struck Spain's pig farmers in the spring of 2010. On 41 farms across the country—each home to between 800 and 3,000 pigs—many sows suddenly ceased bearing young.
On some farms, all the sows stopped reproducing. On others, those that did become pregnant produced smaller litters.
When investigators examined the sows and the semen that had been used to artificially inseminate them—it had been collected from different boar studs and refrigerated—they couldn't find anything wrong. The sperm cells weren't misshapen. None of the sows were diseased. No microbes or fungal toxins were detected in their feed or water.
Only one factor was common to all the farms and studs: The plastic bags used for semen storage all came from the same place.
Investigating those bags has led Cristina Nerín, an analytical chemist at the University of Zaragoza who studies packaging materials, to publish new research that traces the pigs' infertility to chemical compounds in the plastics.
This is "the first time that the correlation between reproductive failures and compounds migrating from plastic materials [has been] studied and demonstrated," says Nerín, whose team published last month in the journal Scientific Reports.
The implications could extend far beyond the farm.
Some of the same chemicals found in the pigs' semen storage bags are routinely used in packaging food for humans and are known to migrate into food. The strange case of the Spanish pigs, Nerín says, "shows the real risks we face." (Explore an interactive showing toxic chemicals that may be lurking in your home.)
Not Just About Pigs
Cyclic lactone, for instance, is a common by-product in adhesives used in potato chip bags and sliced meat packages. It was one of the chemicals found in high levels in the semen bags that had been used on the farms with the highest rates of reproductive failure.
Another chemical found in high levels on those farms: a compound called BADGE, a derivative of the notorious bisphenol A (BPA). It's the building block of epoxy resins that form the basis for 95 percent of food and beverage can linings in the U.S. (Also see "Chemical BPA Linked to Heart Disease, Study Confirms.")
In one recent study led by analytical chemist Kurunthachalam Kannan of the New York State Department of Health in Albany, BADGE, which is also found in household dust, was detected in 100 percent of 127 urine samples collected from people in the U.S. and China.
BPA, the precursor of BADGE, is a known endocrine disruptor: It mimics and interferes with the action of a human hormone, in this case estrogen. A derivative of BADGE called BADGE-2H2O—which forms when BADGE meets water—is an even more potent estrogen mimic.
A lot of research—epidemiological, lab-animal, and clinical studies—has linked endocrine disruptors to adverse health effects, including abnormal testicular development, early puberty, prostate cancer, breast cancer, and even obesity.
Nerín thinks the suspect chemicals in the pigs' bags came from adhesives used to glue together the multilayer plastic that made up the bags. But the chemicals in question aren't normally used for that purpose. Their presence in the Spanish pig semen bags may reflect some kind of unusual contamination.
The supplier of the bags, a company named Magapor, had contacted Nerín because of her expertise. "They were desperate," she says, "because they didn't find a reason why reproduction failed."
Nerín confirmed her suspicion that the high levels of cyclic lactone and BADGE were to blame by "spiking" a new batch of semen with a mix that included those two chemicals and inseminating two groups of 50 sows with either the spiked mixture or a control. Just 58 percent of the sows inseminated with the spiked semen became pregnant, compared with 84 percent of the controls.
Magapor had purchased the semen storage bags from a Chinese manufacturer. When the company switched to a different bag producer, the Spanish pigs' fertility returned to normal.
To complicate the story further, Nerín didn't find any evidence that BADGE was acting as an endocrine disruptor at the levels at which it was present in the semen bags. But lab experiments suggest BADGE is a mutagen as well as an endocrine disruptor: Besides binding to hormone receptors inside cells, it can bind to DNA, causing mutations.
Because the sperm cells in Nerín's pig study looked normal and moved and penetrated eggs normally, she believes many of the pregnancy failures may have resulted from damage to the sperm's DNA—which somehow caused fertilized embryos not to develop normally and not to implant in the sow's uterus.
Effects in Humans?
Meanwhile another paper published last month revealed a specific mechanism by which endocrine disruptors might indeed interfere with fertilization in humans.
One of the authors, physician Niels Skakkebaek of the Rigshospitalet, a university hospital in Copenhagen, has been studying testicular disorders and endocrine disruptors for decades. In a 1992 paper in the British Medical Journal, he reported evidence indicating that sperm quality had deteriorated among men in the United States and elsewhere over the previous 50 years.
In the new study, Skakkebaek; Timo Strünker of the Center of Advanced European Studies and Research in Bonn, Germany; and their colleagues exposed human sperm in lab tests to 96 common endocrine disruptors—chemicals, they write, that are "omnipresent in food, household, and personal care products."
They looked at the effects of the chemicals on a specific signaling conduit in sperm (and other cells) called a calcium channel. The calcium channel in sperm is usually activated by female hormones in the female reproductive tract, including progesterone released by cells surrounding the egg. Activation of the calcium channel allows calcium ions to flood into the sperm cells, which in turn affects their motion, causing them to swim toward an egg and penetrate it.
Skakkebaek and Strünker found that about one-third of the chemicals they tested in the lab evoked a "sizable" response by the calcium channel.
For example, some caused the sperm's tail to curl up rather than flick from side to side. The chemicals that had the strongest effects included ultraviolet light-filtering agents in sunscreens; plastic-softening phthalates used in food and drink containers; and fungicides and antibacterial compounds such as triclosan, which are commonly found in soaps, toothpaste, and toys.
"That was quite unexpected to find so many that could have an effect," Skakkebaek says. "This is the first time this has been shown."
If endocrine-disrupting chemicals are present in the female reproductive tract, Skakkebaek says, they may desensitize the sperm to signals from progesterone. "The sperm cells may have more difficulty in sensing where the egg is," he says. "They could also be swimming in the wrong direction, because they had wrong signals on the way."
That, in turn, might disrupt the process of fertilization.
Skakkebaek's lab tests, like the Spanish semen bags, placed the suspect chemicals in direct contact with sperm cells. But it's not known whether those chemicals are in fact present in the female reproductive tract in dangerous concentrations.
Some researchers question whether everyday exposure to such chemicals in food packaging, say, would have the same detrimental effects on sperm; after the chemicals were ingested, they would be metabolized in the human body, which could change their structure and toxicity.
One skeptic is Allan Pacey, a senior lecturer in andrology at the University of Sheffield in the U.K. He and his co-workers conducted two large epidemiological studies on thousands of British men, examining both occupational exposures to chemicals and lifestyle issues, such as drinking and smoking. They found that only two risk factors—exposure to glycol ether (a paint ingredient) and wearing tight underwear—were associated with "low motile sperm count."
"It is possible to measure effects on ejaculated sperm in the lab, but this is a long way removed from what may be happening in the real world," Pacey says.
Skakkebaek agrees that more studies of how chemical exposure affects actual humans are needed.
"Most of these chemicals are found in almost everybody," he says, referring to the ones in his recent study. "We know for sure that they are in our bodies, because we know for sure that they are excreted in our urine. But what we don't know for sure is the concentration."
As for Nerín's study of the Spanish pigs, "they really found a clear association" between chemical exposure and infertility, Skakkebaek says. "I believe it should be taken as a warning."