A chemical widely found in food packaging and other plastics may cause severe genetic defects in embryos, at levels people are commonly exposed to, according to a scientific study published today.
Laboratory experiments by geneticists at Case Western Reserve University in Ohio showed that bisphenol A disrupts the way that chromosomes align to produce the eggs of mice, leading to aneuploidy, which is the main cause of miscarriages and Down's syndrome in humans.
Scientists say the study is the first to show that exposure to a small amount of an environmental contaminant that mimics the hormone estrogen disrupts the growth of embryos, killing them or leading to genetically abnormal offspring.
Bisphenol A, known as BPA, is used in the manufacture of hard, clear plastics, including containers used to store and microwave food and sealants used on teeth to prevent cavities.
Toxicologists say the chemical leaches from plastic food and drink containers, including baby bottles and cookware, as they age, especially when they are microwaved or cleaned with harsh detergents. BPA also has been found at low levels in water supplies.
The new study showed that when a cell is exposed to BPA, "it looks like someone shot the chromosomes with a shotgun. They are totally disorganized. If you disorganize the chromosomes, it is a death sentence for an embryo," said Frederick vom Saal, a reproductive toxicologist at the University of Missouri. "This is a stunning form of damage. It disrupts development of the cell that becomes your baby."
Plastic-industry representatives have said there are no safety issues related to low exposure, and they have disputed the results of past studies that showed other reproductive effects. Representatives of the Society of the Plastics Industry were unavailable for comment on Monday.
BPA ranks among one of industry's top chemicals, with 2 billion pounds used yearly.
Medical experts say the study is important because they have long tried to unravel the causes of chromosomal defects in humans, known as aneuploidy. An estimated 10% to 25% of fertilized human eggs are aneuploid, and almost all end in miscarriage in the first trimester, often before a woman knows she is pregnant. The rest result in children born with Down's syndrome.
"Our studies have obvious relevance to the genesis of aneuploidy in the human," the scientists wrote in the journal Current Biology. They reported that they found defects in the mice "at exposure levels close to or even below those considered safe" for human exposure.
"The effect is so striking in the mice and so unexpected," Patricia Hunt, who was the lead researcher in the study, said in an interview. "Of course we have no way of knowing that the effect of BPA is exactly the same in humans. But given the striking effects in mice, I'm not sure we can wait to know if mice and humans are exactly the same."
Because the risk of birth defects increases with a mother's age, scientists have long theorized that a mother's fluctuating hormones may be at the root of aneuploidy and birth defects. The new study confirms that there is a hormonal link. In this case, however, the defects were caused by an industrial chemical that mimics estrogen.
The scientists' discovery was accidental. In 1998, at three separate laboratories at the Cleveland-based Case Western, researchers noticed a sudden, large increase in chromosomal abnormalities in the eggs of mice they were using to study aneuploidy and Alzheimer's disease.
The researchers thought the mice were mutants. But they learned a worker had used an improper detergent to clean the plastic mouse cages and water bottles. The detergent was highly alkaline, and it caused large amounts of BPA to leach from the plastic, continuously exposing the mice.
The eggs of mice in these cages had eight times more aneuploidy and 20 times more errors in chromosomal alignment than the eggs of mice not exposed to BPA. The death rate of newborn mice also was higher. When the mice colony was moved to a new facility, the defect rates returned to normal.
The scientists then conducted repeat experiments, feeding mice water contaminated with BPA. The tests confirmed that the chemical altered chromosome alignment at exposures that were low and short in duration, Hunt said. Levels that caused the damaging effects are similar to those found in studies of human exposure in Europe.
The mouse is considered a reliable model for human genetic research. It is useful for studying birth defects in particular because the process of cell division that creates mouse and human eggs is the same.
Previously, scientists, including Vom Saal, have reported other reproductive effects -- enlarged prostates, decreased sperm counts and early puberty -- in mice born to mothers exposed to low levels of BPA. But industry groups disputed the results, saying the effects shown were fairly small and difficult to verify.