A study on the fetuses of pregnant rhesus macaque monkeys has shown that exposure to the chemical bisphenol A, or BPA, led to changes in their lungs that increased the potential for developing asthma.
The study, conducted at the National Primate Research Center at UC Davis, is part of a larger study designed to look at how BPA affects the endocrine system of macaques.
The results of the lung research – considered the first of its kind – adds another layer to the ongoing debate on the effects of BPA, which is found in many products, including on the inside of cans, in plastic bottles, on cash register receipts, and in older plastic baby bottles.
The chemical has been widely studied. Many studies have found a link between BPA and effects on hormonal systems and fetal development.
The results of past studies led many manufacturers to voluntarily remove plastic containing BPA from baby bottles and toddler sippy cups. In 2013, California banned the manufacture and sale of all bottles and cups that contain detectable levels of BPA. The chemical industry has argued that the chemical is safe at the levels humans are exposed to daily.
The UC Davis research on the monkeys offers a compelling and deeper window into the effects of BPA, since most of the lung research done to date on the chemical has been conducted on rodents, said Laura Van Winkle, a toxicologist at UC Davis and lead researcher of the study.
Moreover, the study is seen as important because the fetal development of macaques mirrors that of humans.
"This is the first study to show a cellular and functional change in the lungs of animals exposed to BPA during the third trimester – a critical window of development," Van Winkle said.
Female macaques between 6 and 13 years of age were used in the study. After mating and conception, the macaques received an implant that gave them dosages of BPA to equal the level of BPA found in human blood, Van Winkle said.
"Our model faithfully replicates what is known for human exposure levels, and this is an environmentally relevant level," said Van Winkle. "Also, we did a constant exposure because human studies have shown people have nearly constant levels in their blood."
Fifteen macaques were used in the study; six were dosed with BPA, and the others were in a control group. Tissue samples were collected from their fetuses after they were removed by cesarean section and put down. Tissues from the fetuses of macaques exposed to BPA showed genetic signs that would lead to an acceleration in the development of mucus-secretion cells in lung airways.
"Those cells are important for normal cell function, but too many of those cells have been correlated with airway diseases," Van Winkle said.
Prenatal exposure to BPA disturbs the course of development, Van Winkle said.
The link between BPA and asthma is no small matter for the Central Valley, where asthma rates are higher than anywhere else in California.
"This is a significant study," said Sanjay Jhawar, a professor of pediatric medicine at UC Davis Health System who specializes in childhood asthma.
"There is a high rate of asthma in the Central Valley, because of the high number of allergens here," Jhawar said. "So this is a good study from various clinical points of view."
"Some of the significant respiratory symptoms that happen in neonates and infants are related to secretions, and exposure to BPA might have a role to play, which as yet has not been proven in human beings," Jhawar said.
Each year, there are roughly 189,700 new cases of asthma diagnosed in California, according to state data. Asthma diagnoses are rising in the state and the nation.
In Sacramento County, 12.7 percent of children have lifetime asthma – below the statewide average of 14.2 percent – according to the 2009 California Health Interview Survey. That number has risen from 9.1 percent in 2007.
But the 2009 survey found that many Central Valley counties have much higher rates than the state average, such as Yuba at 23.9 percent, Colusa at 23.7 percent and Fresno at 19.2 percent.
"The BPA field has been getting more and more interesting because all of these studies suggest a lot of different fetal effects," said Patricia Hunt, a professor of reproductive biology at Washington State University, and a co-investigator of the larger macaque study.
"What was found with the lung is very interesting because this had never been reported," she said. "While there is a lot of information on reproduction and the development of the brain, there's just really not anything known about the lung."
The lung study piggybacks off a larger study on the effects of BPA on macaque fetuses.
That study found that BPA had adverse effects elsewhere – most significantly on ovary development. The ovary study found that exposure to BPA disrupted the development of the ovaries – a significant finding because ovarian development occurs prenatally and the number of eggs a female will have later in life is established at birth, Van Winkle said.
Like the study on lung tissue development, the ovary study is seen as significant because the effects are indicative of how BPA may affect human fetuses.
"We have analyzed the results from these various studies, and we now know that some animals have certain tissues affected more than others," said Catherine VandeVoort, a professor of obstetrics and gynecology at the Primate Research Center and leader of the ovary study.
"Some animals had greater effects in the ovary or mammary gland, while a different set of animals showed greater effects in the brain or lung," VandeVoort said. "All animals were affected by BPA, but there were individual differences in what tissues were most affected."
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